Variant chr19-48165573-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.322

Variant links:

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]

LIG1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 linkuse as main transcript	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 linkuse as main transcript	c.-7C>T		5_prime_UTR_variant	2/28	1	NM_000234.3	P4	P18858-1

Frequencies

GnomAD3 genomes

AF:

0.168

AC:

25446

AN:

151886

Hom.:

2515

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.125

AC XY:

91054

AN XY:

726804

show subpopulations

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.:

AF XY:

0.164

AC XY:

12150

AN XY:

74294

show subpopulations

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

LINK: link

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 -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over