Variant 19-48151296-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000234.3(LIG1):c.510C>A(p.Ala170Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 1,610,878 control chromosomes in the GnomAD database, including 195,168 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.50 ( 19396 hom., cov: 29)

Exomes 𝑓: 0.49 ( 175772 hom. )

Consequence

LIG1
NM_000234.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.130

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:

LIG1 (HGNC:):

LIG1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 19-48151296-G-T is Benign according to our data. Variant chr19-48151296-G-T is described in ClinVar as [Benign]. Clinvar id is 403037.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.13 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIG1	NM_000234.3 linkuse as main transcript	c.510C>A	p.Ala170Ala	synonymous_variant	7/28	ENST00000263274.12	NP_000225.1	P18858-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIG1	ENST00000263274.12 linkuse as main transcript	c.510C>A	p.Ala170Ala	synonymous_variant	7/28	1	NM_000234.3	ENSP00000263274.6		P18858-1

Frequencies

GnomAD3 genomes

AF:

0.502

AC:

76155

AN:

151572

Hom.:

19373

Cov.:

show subpopulations

Gnomad AFR

AF:

0.546

Gnomad AMI

AF:

0.378

Gnomad AMR

AF:

0.443

Gnomad ASJ

AF:

0.412

Gnomad EAS

AF:

0.673

Gnomad SAS

AF:

0.402

Gnomad FIN

AF:

0.518

Gnomad MID

AF:

0.402

Gnomad NFE

AF:

0.488

Gnomad OTH

AF:

0.491

GnomAD3 exomes

AF:

0.488

AC:

122770

AN:

251442

Hom.:

30713

AF XY:

0.483

AC XY:

65655

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.554

Gnomad AMR exome

AF:

0.436

Gnomad ASJ exome

AF:

0.414

Gnomad EAS exome

AF:

0.706

Gnomad SAS exome

AF:

0.403

Gnomad FIN exome

AF:

0.512

Gnomad NFE exome

AF:

0.486

Gnomad OTH exome

AF:

0.467

GnomAD4 exome

AF:

0.488

AC:

712022

AN:

1459190

Hom.:

175772

Cov.:

AF XY:

0.485

AC XY:

352052

AN XY:

726052

show subpopulations

Gnomad4 AFR exome

AF:

0.541

Gnomad4 AMR exome

AF:

0.437

Gnomad4 ASJ exome

AF:

0.414

Gnomad4 EAS exome

AF:

0.664

Gnomad4 SAS exome

AF:

0.397

Gnomad4 FIN exome

AF:

0.506

Gnomad4 NFE exome

AF:

0.490

Gnomad4 OTH exome

AF:

0.494

GnomAD4 genome

AF:

0.503

AC:

76229

AN:

151688

Hom.:

19396

Cov.:

AF XY:

0.500

AC XY:

37051

AN XY:

74102

show subpopulations

Gnomad4 AFR

AF:

0.546

Gnomad4 AMR

AF:

0.443

Gnomad4 ASJ

AF:

0.412

Gnomad4 EAS

AF:

0.674

Gnomad4 SAS

AF:

0.404

Gnomad4 FIN

AF:

0.518

Gnomad4 NFE

AF:

0.488

Gnomad4 OTH

AF:

0.491

Alfa

AF:

0.488

Hom.:

35623

Bravo

AF:

0.505

Asia WGS

AF:

0.574

AC:

1994

AN:

3478

EpiCase

AF:

0.481

EpiControl

AF:

0.476

ClinVar

Significance: Benign

Submissions summary: Benign:4

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 72% of patients studied by a panel of primary immunodeficiencies. Number of patients: 69. 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:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.8

DANN

Benign

0.48

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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