rs20579

Variant names:

• chr19-48165573-G-A
• rs20579
• NM_000234.3:c.-7C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-48165573-G-A
• chr19-48165573-G-C
• chr19-48165573-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.-7C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 1,612,808 control chromosomes in the GnomAD database, including 15,012 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2516 hom., cov: 31)
  • Exomes 𝑓: 0.13 (12496 hom.)
• Consequence: LIG1 NM_000234.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.322

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=-0.87).
• BP6: Variant 19-48165573-G-A is Benign according to our data. Variant chr19-48165573-G-A is described in ClinVar as [Benign]. Clinvar id is 403039.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIG1	NM_000234.3	c.-7C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 28	ENST00000263274.12	NP_000225.1
LIG1	NM_000234.3	c.-7C>T		5_prime_UTR_variant	Exon 2 of 28	ENST00000263274.12	NP_000225.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIG1	ENST00000263274.12	c.-7C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 28	1	NM_000234.3	ENSP00000263274.6
LIG1	ENST00000263274.12	c.-7C>T		5_prime_UTR_variant	Exon 2 of 28	1	NM_000234.3	ENSP00000263274.6

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25446 AN: 151886 Hom.: 2515 Cov.: 31

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.0940

Gnomad FIN AF: 0.0877

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.153

GnomAD3 exomes AF: 0.133 AC: 33504 AN: 251480 Hom.: 2612 AF XY: 0.128 AC XY: 17459 AN XY: 135910

Gnomad AFR exome AF: 0.296

Gnomad AMR exome AF: 0.152

Gnomad ASJ exome AF: 0.113

Gnomad EAS exome AF: 0.129

Gnomad SAS exome AF: 0.101

Gnomad FIN exome AF: 0.0953

Gnomad NFE exome AF: 0.123

Gnomad OTH exome AF: 0.130

GnomAD4 exome AF: 0.126 AC: 184635 AN: 1460804 Hom.: 12496 Cov.: 33 AF XY: 0.125 AC XY: 91054 AN XY: 726804

Gnomad4 AFR exome AF: 0.289

Gnomad4 AMR exome AF: 0.153

Gnomad4 ASJ exome AF: 0.113

Gnomad4 EAS exome AF: 0.0929

Gnomad4 SAS exome AF: 0.0995

Gnomad4 FIN exome AF: 0.0961

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.134

GnomAD4 genome AF: 0.168 AC: 25468 AN: 152004 Hom.: 2516 Cov.: 31 AF XY: 0.164 AC XY: 12150 AN XY: 74294

Gnomad4 AFR AF: 0.284

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.0937

Gnomad4 FIN AF: 0.0877

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.152

Alfa AF: 0.143 Hom.: 1226

Bravo AF: 0.180

Asia WGS AF: 0.124 AC: 431 AN: 3478

EpiCase AF: 0.121

EpiControl AF: 0.124

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

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 -

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. -

not provided Benign:1

-

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	-0.87
CADD	Benign	12
DANN	Benign	0.83
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.1

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: rs20579; hg19: chr19-48668830; COSMIC: COSV54391878;