19-48128151-C-T

Variant names:

• chr19-48128151-C-T
• rs156641
• NM_000234.3:c.1822-131G>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.1822-131G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 740,756 control chromosomes in the GnomAD database, including 49,091 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.30 (7915 hom., cov: 31)
  • Exomes 𝑓: 0.37 (41176 hom.)
• Consequence: LIG1 NM_000234.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.349
• Publications: 22 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=-0.82).
• BP6: Variant 19-48128151-C-T is Benign according to our data. Variant chr19-48128151-C-T is described in ClinVar as Benign. ClinVar VariationId is 2628277.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIG1	NM_000234.3	c.1822-131G>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.1822-131G>A		intron_variant	Intron 19 of 27	1	NM_000234.3	ENSP00000263274.6

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45476 AN: 151858 Hom.: 7910 Cov.: 31

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.324

GnomAD4 exome AF: 0.366 AC: 215208 AN: 588780 Hom.: 41176 AF XY: 0.365 AC XY: 116214 AN XY: 318462

African (AFR) AF: 0.122 AC: 2013 AN: 16530

American (AMR) AF: 0.292 AC: 10417 AN: 35628

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 6364 AN: 20070

East Asian (EAS) AF: 0.565 AC: 19028 AN: 33680

South Asian (SAS) AF: 0.320 AC: 20871 AN: 65140

European-Finnish (FIN) AF: 0.411 AC: 16371 AN: 39824

Middle Eastern (MID) AF: 0.302 AC: 1182 AN: 3916

European-Non Finnish (NFE) AF: 0.373 AC: 127609 AN: 342268

Other (OTH) AF: 0.358 AC: 11353 AN: 31724

GnomAD4 genome AF: 0.299 AC: 45497 AN: 151976 Hom.: 7915 Cov.: 31 AF XY: 0.302 AC XY: 22462 AN XY: 74302

African (AFR) AF: 0.120 AC: 4975 AN: 41460

American (AMR) AF: 0.278 AC: 4247 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 1061 AN: 3468

East Asian (EAS) AF: 0.554 AC: 2863 AN: 5166

South Asian (SAS) AF: 0.328 AC: 1576 AN: 4810

European-Finnish (FIN) AF: 0.430 AC: 4550 AN: 10580

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.371 AC: 25173 AN: 67912

Other (OTH) AF: 0.325 AC: 684 AN: 2106

Alfa AF: 0.346 Hom.: 7261

Bravo AF: 0.284

Asia WGS AF: 0.444 AC: 1542 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 23% of patients studied by a panel of primary immunodeficiencies. Number of patients: 22. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.80
DANN	Benign	0.64
PhyloP100		-0.35
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: rs156641; hg19: chr19-48631408; COSMIC: COSV54390776; COSMIC: COSV54390776;