rs3730849

Variant names:

• chr19-48165538-G-A
• rs3730849
• NM_000234.3:c.17+12C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-48165538-G-A
• chr19-48165538-G-C
• chr19-48165538-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000234.3(LIG1):​c.17+12C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 1,596,792 control chromosomes in the GnomAD database, including 111,129 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (8109 hom., cov: 31)
  • Exomes 𝑓: 0.37 (103020 hom.)
• Consequence: LIG1 NM_000234.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.22

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 19-48165538-G-A is Benign according to our data. Variant chr19-48165538-G-A is described in ClinVar as [Benign]. Clinvar id is 403038.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIG1	NM_000234.3	c.17+12C>T		intron_variant	Intron 2 of 27	ENST00000263274.12	NP_000225.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIG1	ENST00000263274.12	c.17+12C>T		intron_variant	Intron 2 of 27	1	NM_000234.3	ENSP00000263274.6

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45850 AN: 151714 Hom.: 8106 Cov.: 31

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.321

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.330

GnomAD3 exomes AF: 0.359 AC: 90308 AN: 251440 Hom.: 17560 AF XY: 0.363 AC XY: 49336 AN XY: 135898

Gnomad AFR exome AF: 0.108

Gnomad AMR exome AF: 0.294

Gnomad ASJ exome AF: 0.330

Gnomad EAS exome AF: 0.574

Gnomad SAS exome AF: 0.317

Gnomad FIN exome AF: 0.426

Gnomad NFE exome AF: 0.381

Gnomad OTH exome AF: 0.359

GnomAD4 exome AF: 0.371 AC: 535969 AN: 1444960 Hom.: 103020 Cov.: 30 AF XY: 0.370 AC XY: 266516 AN XY: 719868

Gnomad4 AFR exome AF: 0.101

Gnomad4 AMR exome AF: 0.294

Gnomad4 ASJ exome AF: 0.328

Gnomad4 EAS exome AF: 0.558

Gnomad4 SAS exome AF: 0.311

Gnomad4 FIN exome AF: 0.419

Gnomad4 NFE exome AF: 0.380

Gnomad4 OTH exome AF: 0.364

GnomAD4 genome AF: 0.302 AC: 45867 AN: 151832 Hom.: 8109 Cov.: 31 AF XY: 0.305 AC XY: 22647 AN XY: 74164

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.290

Gnomad4 ASJ AF: 0.316

Gnomad4 EAS AF: 0.548

Gnomad4 SAS AF: 0.316

Gnomad4 FIN AF: 0.431

Gnomad4 NFE AF: 0.377

Gnomad4 OTH AF: 0.330

Alfa AF: 0.339 Hom.: 2077

Bravo AF: 0.287

Asia WGS AF: 0.435 AC: 1510 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 57% of patients studied by a panel of primary immunodeficiencies. Number of patients: 55. 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	-0.90
CADD	Benign	0.066
DANN	Benign	0.57

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: rs3730849; hg19: chr19-48668795;