rs3731007

Variant names:

• chr19-48123347-G-A
• rs3731007
• NM_000234.3:c.2005-29C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000234.3(LIG1):​c.2005-29C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0807 in 1,608,704 control chromosomes in the GnomAD database, including 9,200 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.15 (2817 hom., cov: 31)
  • Exomes 𝑓: 0.073 (6383 hom.)
• Consequence: LIG1 NM_000234.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.436
• Publications: 13 publications found

Genes affected

LIG1 (HGNC:6598): (DNA ligase 1) This gene encodes a member of the ATP-dependent DNA ligase protein family. The encoded protein functions in DNA replication, recombination, and the base excision repair process. Mutations in this gene that lead to DNA ligase I deficiency result in immunodeficiency and increased sensitivity to DNA-damaging agents. Disruption of this gene may also be associated with a variety of cancers. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

LIG1 Gene-Disease associations (from GenCC):

• immunodeficiency 96

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000269534 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 2 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 19-48123347-G-A is Benign according to our data. Variant chr19-48123347-G-A is described in CliVar as Benign. Clinvar id is 2688333.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48123347-G-A is described in CliVar as Benign. Clinvar id is 2688333.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48123347-G-A is described in CliVar as Benign. Clinvar id is 2688333.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48123347-G-A is described in CliVar as Benign. Clinvar id is 2688333.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48123347-G-A is described in CliVar as Benign. Clinvar id is 2688333.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48123347-G-A is described in CliVar as Benign. Clinvar id is 2688333.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48123347-G-A is described in CliVar as Benign. Clinvar id is 2688333.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48123347-G-A is described in CliVar as Benign. Clinvar id is 2688333.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48123347-G-A is described in CliVar as Benign. Clinvar id is 2688333.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48123347-G-A is described in CliVar as Benign. Clinvar id is 2688333.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48123347-G-A is described in CliVar as Benign. Clinvar id is 2688333.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48123347-G-A is described in CliVar as Benign. Clinvar id is 2688333.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48123347-G-A is described in CliVar as Benign. Clinvar id is 2688333.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48123347-G-A is described in CliVar as Benign. Clinvar id is 2688333.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48123347-G-A is described in CliVar as Benign. Clinvar id is 2688333.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48123347-G-A is described in CliVar as Benign. Clinvar id is 2688333.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48123347-G-A is described in CliVar as Benign. Clinvar id is 2688333.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48123347-G-A is described in CliVar as Benign. Clinvar id is 2688333.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48123347-G-A is described in CliVar as Benign. Clinvar id is 2688333.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48123347-G-A is described in CliVar as Benign. Clinvar id is 2688333.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48123347-G-A is described in CliVar as Benign. Clinvar id is 2688333.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48123347-G-A is described in CliVar as Benign. Clinvar id is 2688333.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48123347-G-A is described in CliVar as Benign. Clinvar id is 2688333.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48123347-G-A is described in CliVar as Benign. Clinvar id is 2688333.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48123347-G-A is described in CliVar as Benign. Clinvar id is 2688333.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48123347-G-A is described in CliVar as Benign. Clinvar id is 2688333.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48123347-G-A is described in CliVar as Benign. Clinvar id is 2688333.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48123347-G-A is described in CliVar as Benign. Clinvar id is 2688333.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48123347-G-A is described in CliVar as Benign. Clinvar id is 2688333.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48123347-G-A is described in CliVar as Benign. Clinvar id is 2688333.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48123347-G-A is described in CliVar as Benign. Clinvar id is 2688333.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48123347-G-A is described in CliVar as Benign. Clinvar id is 2688333.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48123347-G-A is described in CliVar as Benign. Clinvar id is 2688333.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48123347-G-A is described in CliVar as Benign. Clinvar id is 2688333.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48123347-G-A is described in CliVar as Benign. Clinvar id is 2688333.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48123347-G-A is described in CliVar as Benign. Clinvar id is 2688333.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48123347-G-A is described in CliVar as Benign. Clinvar id is 2688333.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48123347-G-A is described in CliVar as Benign. Clinvar id is 2688333.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48123347-G-A is described in CliVar as Benign. Clinvar id is 2688333.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48123347-G-A is described in CliVar as Benign. Clinvar id is 2688333.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48123347-G-A is described in CliVar as Benign. Clinvar id is 2688333.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48123347-G-A is described in CliVar as Benign. Clinvar id is 2688333.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48123347-G-A is described in CliVar as Benign. Clinvar id is 2688333.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48123347-G-A is described in CliVar as Benign. Clinvar id is 2688333.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIG1	NM_000234.3	c.2005-29C>T		intron_variant	Intron 21 of 27	ENST00000263274.12	NP_000225.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIG1	ENST00000263274.12	c.2005-29C>T		intron_variant	Intron 21 of 27	1	NM_000234.3	ENSP00000263274.6

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22698 AN: 152008 Hom.: 2818 Cov.: 31

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.0884

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.0665

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.0568

Gnomad OTH AF: 0.132

GnomAD2 exomes AF: 0.103 AC: 25379 AN: 245830 AF XY: 0.101

Gnomad AFR exome AF: 0.340

Gnomad AMR exome AF: 0.0824

Gnomad ASJ exome AF: 0.0871

Gnomad EAS exome AF: 0.175

Gnomad FIN exome AF: 0.0712

Gnomad NFE exome AF: 0.0586

Gnomad OTH exome AF: 0.103

GnomAD4 exome AF: 0.0735 AC: 107037 AN: 1456578 Hom.: 6383 Cov.: 31 AF XY: 0.0751 AC XY: 54414 AN XY: 724842

African (AFR) AF: 0.357 AC: 11938 AN: 33424

American (AMR) AF: 0.0880 AC: 3935 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.0852 AC: 2225 AN: 26126

East Asian (EAS) AF: 0.202 AC: 8020 AN: 39690

South Asian (SAS) AF: 0.147 AC: 12647 AN: 86192

European-Finnish (FIN) AF: 0.0671 AC: 3282 AN: 48944

Middle Eastern (MID) AF: 0.158 AC: 911 AN: 5762

European-Non Finnish (NFE) AF: 0.0524 AC: 58271 AN: 1111400

Other (OTH) AF: 0.0963 AC: 5808 AN: 60332

GnomAD4 genome AF: 0.149 AC: 22713 AN: 152126 Hom.: 2817 Cov.: 31 AF XY: 0.148 AC XY: 11019 AN XY: 74374

African (AFR) AF: 0.338 AC: 13993 AN: 41460

American (AMR) AF: 0.109 AC: 1667 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0884 AC: 307 AN: 3472

East Asian (EAS) AF: 0.194 AC: 1000 AN: 5166

South Asian (SAS) AF: 0.146 AC: 702 AN: 4810

European-Finnish (FIN) AF: 0.0665 AC: 705 AN: 10606

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.0568 AC: 3863 AN: 68006

Other (OTH) AF: 0.133 AC: 281 AN: 2108

Alfa AF: 0.109 Hom.: 531

Bravo AF: 0.160

Asia WGS AF: 0.166 AC: 578 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 21% of patients studied by a panel of primary immunodeficiencies. Number of patients: 20. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.2
DANN	Benign	0.64
PhyloP100		-0.44
BranchPoint Hunter		2.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3731007; hg19: chr19-48626604; COSMIC: COSV54390204; COSMIC: COSV54390204;