rs20579

chr19-48165573-G-Achr19-48165573-G-C

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 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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/exons	MANE	UniProt
LIG1	NM_000234.3	c.-7C>T		5_prime_UTR_variant	2/28	ENST00000263274.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIG1	ENST00000263274.12	c.-7C>T		5_prime_UTR_variant	2/28	1	NM_000234.3	P4

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Nov 12, 2023	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. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	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 -

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;