19-48131041-C-T

Variant names:

• chr19-48131041-C-T
• rs3730994
• NM_000234.3:c.1821+35G>A

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.1821+35G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 1,562,268 control chromosomes in the GnomAD database, including 12,229 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (2059 hom., cov: 33)
  • Exomes 𝑓: 0.12 (10170 hom.)
• Consequence: LIG1 NM_000234.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.628
• Publications: 4 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 19-48131041-C-T is Benign according to our data. Variant chr19-48131041-C-T is described in CliVar as Benign. Clinvar id is 2628267.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48131041-C-T is described in CliVar as Benign. Clinvar id is 2628267.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48131041-C-T is described in CliVar as Benign. Clinvar id is 2628267.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48131041-C-T is described in CliVar as Benign. Clinvar id is 2628267.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48131041-C-T is described in CliVar as Benign. Clinvar id is 2628267.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48131041-C-T is described in CliVar as Benign. Clinvar id is 2628267.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48131041-C-T is described in CliVar as Benign. Clinvar id is 2628267.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48131041-C-T is described in CliVar as Benign. Clinvar id is 2628267.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48131041-C-T is described in CliVar as Benign. Clinvar id is 2628267.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48131041-C-T is described in CliVar as Benign. Clinvar id is 2628267.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48131041-C-T is described in CliVar as Benign. Clinvar id is 2628267.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48131041-C-T is described in CliVar as Benign. Clinvar id is 2628267.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48131041-C-T is described in CliVar as Benign. Clinvar id is 2628267.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48131041-C-T is described in CliVar as Benign. Clinvar id is 2628267.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48131041-C-T is described in CliVar as Benign. Clinvar id is 2628267.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48131041-C-T is described in CliVar as Benign. Clinvar id is 2628267.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48131041-C-T is described in CliVar as Benign. Clinvar id is 2628267.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48131041-C-T is described in CliVar as Benign. Clinvar id is 2628267.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48131041-C-T is described in CliVar as Benign. Clinvar id is 2628267.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48131041-C-T is described in CliVar as Benign. Clinvar id is 2628267.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48131041-C-T is described in CliVar as Benign. Clinvar id is 2628267.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48131041-C-T is described in CliVar as Benign. Clinvar id is 2628267.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48131041-C-T is described in CliVar as Benign. Clinvar id is 2628267.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48131041-C-T is described in CliVar as Benign. Clinvar id is 2628267.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48131041-C-T is described in CliVar as Benign. Clinvar id is 2628267.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48131041-C-T is described in CliVar as Benign. Clinvar id is 2628267.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48131041-C-T is described in CliVar as Benign. Clinvar id is 2628267.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48131041-C-T is described in CliVar as Benign. Clinvar id is 2628267.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48131041-C-T is described in CliVar as Benign. Clinvar id is 2628267.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48131041-C-T is described in CliVar as Benign. Clinvar id is 2628267.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48131041-C-T is described in CliVar as Benign. Clinvar id is 2628267.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48131041-C-T is described in CliVar as Benign. Clinvar id is 2628267.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48131041-C-T is described in CliVar as Benign. Clinvar id is 2628267.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48131041-C-T is described in CliVar as Benign. Clinvar id is 2628267.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48131041-C-T is described in CliVar as Benign. Clinvar id is 2628267.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48131041-C-T is described in CliVar as Benign. Clinvar id is 2628267.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48131041-C-T is described in CliVar as Benign. Clinvar id is 2628267.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48131041-C-T is described in CliVar as Benign. Clinvar id is 2628267.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48131041-C-T is described in CliVar as Benign. Clinvar id is 2628267.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48131041-C-T is described in CliVar as Benign. Clinvar id is 2628267.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48131041-C-T is described in CliVar as Benign. Clinvar id is 2628267.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48131041-C-T is described in CliVar as Benign. Clinvar id is 2628267.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48131041-C-T is described in CliVar as Benign. Clinvar id is 2628267.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-48131041-C-T is described in CliVar as Benign. Clinvar id is 2628267.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIG1	NM_000234.3	c.1821+35G>A		intron_variant	Intron 19 of 27	ENST00000263274.12	NP_000225.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIG1	ENST00000263274.12	c.1821+35G>A		intron_variant	Intron 19 of 27	1	NM_000234.3	ENSP00000263274.6

Frequencies

GnomAD3 genomes AF: 0.151 AC: 23019 AN: 152166 Hom.: 2052 Cov.: 33

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.0899

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.0806

Gnomad FIN AF: 0.0867

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.126

GnomAD2 exomes AF: 0.119 AC: 29824 AN: 250316 AF XY: 0.114

Gnomad AFR exome AF: 0.264

Gnomad AMR exome AF: 0.135

Gnomad ASJ exome AF: 0.0836

Gnomad EAS exome AF: 0.126

Gnomad FIN exome AF: 0.0887

Gnomad NFE exome AF: 0.112

Gnomad OTH exome AF: 0.108

GnomAD4 exome AF: 0.117 AC: 164332 AN: 1409984 Hom.: 10170 Cov.: 23 AF XY: 0.115 AC XY: 80817 AN XY: 704408

African (AFR) AF: 0.263 AC: 8548 AN: 32468

American (AMR) AF: 0.135 AC: 6012 AN: 44632

Ashkenazi Jewish (ASJ) AF: 0.0857 AC: 2211 AN: 25790

East Asian (EAS) AF: 0.0979 AC: 3861 AN: 39448

South Asian (SAS) AF: 0.0819 AC: 6981 AN: 85280

European-Finnish (FIN) AF: 0.0909 AC: 4831 AN: 53170

Middle Eastern (MID) AF: 0.0784 AC: 443 AN: 5650

European-Non Finnish (NFE) AF: 0.117 AC: 124415 AN: 1064896

Other (OTH) AF: 0.120 AC: 7030 AN: 58650

GnomAD4 genome AF: 0.151 AC: 23051 AN: 152284 Hom.: 2059 Cov.: 33 AF XY: 0.148 AC XY: 11053 AN XY: 74460

African (AFR) AF: 0.255 AC: 10588 AN: 41540

American (AMR) AF: 0.133 AC: 2034 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0899 AC: 312 AN: 3472

East Asian (EAS) AF: 0.119 AC: 618 AN: 5178

South Asian (SAS) AF: 0.0803 AC: 388 AN: 4832

European-Finnish (FIN) AF: 0.0867 AC: 920 AN: 10616

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7840 AN: 68022

Other (OTH) AF: 0.126 AC: 266 AN: 2114

Alfa AF: 0.107 Hom.: 581

Bravo AF: 0.160

Asia WGS AF: 0.122 AC: 424 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Nov 12, 2023

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 24% of patients studied by a panel of primary immunodeficiencies. Number of patients: 23. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.1
DANN	Benign	0.64
PhyloP100		-0.63
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: rs3730994; hg19: chr19-48634298; COSMIC: COSV54392490; COSMIC: COSV54392490;