NM_000234.3:c.2406T>C

Variant names:

• chr19-48119170-A-G
• rs20581
• NM_000234.3:c.2406T>C

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.2406T>C​(p.Asp802Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 1,581,660 control chromosomes in the GnomAD database, including 259,611 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.64 (32670 hom., cov: 32)
  • Exomes 𝑓: 0.56 (226941 hom.)
• Consequence: LIG1 NM_000234.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.84

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]

ENSG00000269534 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 19-48119170-A-G is Benign according to our data. Variant chr19-48119170-A-G is described in ClinVar as [Benign]. Clinvar id is 403034.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.84 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.846 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIG1	NM_000234.3	c.2406T>C	p.Asp802Asp	synonymous_variant	Exon 25 of 28	ENST00000263274.12	NP_000225.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIG1	ENST00000263274.12	c.2406T>C	p.Asp802Asp	synonymous_variant	Exon 25 of 28	1	NM_000234.3	ENSP00000263274.6

Frequencies

GnomAD3 genomes AF: 0.640 AC: 97228 AN: 152010 Hom.: 32620 Cov.: 32

Gnomad AFR AF: 0.846

Gnomad AMI AF: 0.527

Gnomad AMR AF: 0.542

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.868

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.614

GnomAD3 exomes AF: 0.576 AC: 115798 AN: 201046 Hom.: 34721 AF XY: 0.570 AC XY: 61578 AN XY: 107956

Gnomad AFR exome AF: 0.853

Gnomad AMR exome AF: 0.506

Gnomad ASJ exome AF: 0.484

Gnomad EAS exome AF: 0.878

Gnomad SAS exome AF: 0.554

Gnomad FIN exome AF: 0.574

Gnomad NFE exome AF: 0.530

Gnomad OTH exome AF: 0.557

GnomAD4 exome AF: 0.558 AC: 797677 AN: 1429532 Hom.: 226941 Cov.: 43 AF XY: 0.557 AC XY: 394179 AN XY: 708144

Gnomad4 AFR exome AF: 0.861

Gnomad4 AMR exome AF: 0.515

Gnomad4 ASJ exome AF: 0.483

Gnomad4 EAS exome AF: 0.866

Gnomad4 SAS exome AF: 0.548

Gnomad4 FIN exome AF: 0.571

Gnomad4 NFE exome AF: 0.541

Gnomad4 OTH exome AF: 0.584

GnomAD4 genome AF: 0.640 AC: 97333 AN: 152128 Hom.: 32670 Cov.: 32 AF XY: 0.637 AC XY: 47381 AN XY: 74366

Gnomad4 AFR AF: 0.846

Gnomad4 AMR AF: 0.542

Gnomad4 ASJ AF: 0.482

Gnomad4 EAS AF: 0.868

Gnomad4 SAS AF: 0.555

Gnomad4 FIN AF: 0.583

Gnomad4 NFE AF: 0.544

Gnomad4 OTH AF: 0.615

Alfa AF: 0.556 Hom.: 27181

Bravo AF: 0.651

Asia WGS AF: 0.745 AC: 2590 AN: 3478

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 74% of patients studied by a panel of primary immunodeficiencies. Number of patients: 71. 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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.076
DANN	Benign	0.45
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs20581; hg19: chr19-48622427; COSMIC: COSV54391114; COSMIC: COSV54391114;