rs13436

Variant names:

• chr19-48117779-C-G
• rs13436
• NM_000234.3:c.2442G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-48117779-C-G
• chr19-48117779-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000234.3(LIG1):​c.2442G>C​(p.Ala814Ala) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 1,611,088 control chromosomes in the GnomAD database, including 162,858 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.47 (17579 hom., cov: 34)
  • Exomes 𝑓: 0.44 (145279 hom.)
• Consequence: LIG1 NM_000234.3 splice_region, synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.688

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 19-48117779-C-G is Benign according to our data. Variant chr19-48117779-C-G is described in ClinVar as [Benign]. Clinvar id is 403033.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.688 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIG1	NM_000234.3	c.2442G>C	p.Ala814Ala	splice_region_variant, synonymous_variant	Exon 26 of 28	ENST00000263274.12	NP_000225.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIG1	ENST00000263274.12	c.2442G>C	p.Ala814Ala	splice_region_variant, synonymous_variant	Exon 26 of 28	1	NM_000234.3	ENSP00000263274.6

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72135 AN: 152012 Hom.: 17560 Cov.: 34

Gnomad AFR AF: 0.544

Gnomad AMI AF: 0.461

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.750

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.497

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.428

Gnomad OTH AF: 0.479

GnomAD3 exomes AF: 0.463 AC: 113343 AN: 244628 Hom.: 27359 AF XY: 0.464 AC XY: 61256 AN XY: 132114

Gnomad AFR exome AF: 0.541

Gnomad AMR exome AF: 0.374

Gnomad ASJ exome AF: 0.404

Gnomad EAS exome AF: 0.754

Gnomad SAS exome AF: 0.476

Gnomad FIN exome AF: 0.492

Gnomad NFE exome AF: 0.429

Gnomad OTH exome AF: 0.453

GnomAD4 exome AF: 0.441 AC: 643367 AN: 1458958 Hom.: 145279 Cov.: 46 AF XY: 0.442 AC XY: 320384 AN XY: 725416

Gnomad4 AFR exome AF: 0.547

Gnomad4 AMR exome AF: 0.381

Gnomad4 ASJ exome AF: 0.398

Gnomad4 EAS exome AF: 0.769

Gnomad4 SAS exome AF: 0.468

Gnomad4 FIN exome AF: 0.483

Gnomad4 NFE exome AF: 0.424

Gnomad4 OTH exome AF: 0.461

GnomAD4 genome AF: 0.475 AC: 72196 AN: 152130 Hom.: 17579 Cov.: 34 AF XY: 0.475 AC XY: 35353 AN XY: 74384

Gnomad4 AFR AF: 0.544

Gnomad4 AMR AF: 0.402

Gnomad4 ASJ AF: 0.393

Gnomad4 EAS AF: 0.750

Gnomad4 SAS AF: 0.474

Gnomad4 FIN AF: 0.497

Gnomad4 NFE AF: 0.428

Gnomad4 OTH AF: 0.481

Alfa AF: 0.400 Hom.: 3715

Bravo AF: 0.474

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

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 60% of patients studied by a panel of primary immunodeficiencies. Number of patients: 58. Only high quality variants are reported. -

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	8.5
DANN	Benign	0.78

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

Publications

LitVar

Other links and lift over

dbSNP: rs13436; hg19: chr19-48621036; COSMIC: COSV54392236; COSMIC: COSV54392236;