Variant chr19-48131062-T-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.1821+14A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 1,607,394 control chromosomes in the GnomAD database, including 163,625 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 17799 hom., cov: 33)

Exomes 𝑓: 0.44 ( 145826 hom. )

Consequence

LIG1
NM_000234.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.844

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 19-48131062-T-A is Benign according to our data. Variant chr19-48131062-T-A is described in ClinVar as [Benign]. Clinvar id is 403035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.729 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.1821+14A>T		intron_variant		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.1821+14A>T		intron_variant		1	NM_000234.3	ENSP00000263274.6		P18858-1

Frequencies

GnomAD3 genomes

AF:

0.477

AC:

72544

AN:

152000

Hom.:

17776

Cov.:

show subpopulations

Gnomad AFR

AF:

0.554

Gnomad AMI

AF:

0.459

Gnomad AMR

AF:

0.402

Gnomad ASJ

AF:

0.395

Gnomad EAS

AF:

0.748

Gnomad SAS

AF:

0.474

Gnomad FIN

AF:

0.498

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.428

Gnomad OTH

AF:

0.478

GnomAD3 exomes

AF:

0.466

AC:

116885

AN:

250854

Hom.:

28514

AF XY:

0.467

AC XY:

63273

AN XY:

135626

show subpopulations

Gnomad AFR exome

AF:

0.554

Gnomad AMR exome

AF:

0.376

Gnomad ASJ exome

AF:

0.406

Gnomad EAS exome

AF:

0.755

Gnomad SAS exome

AF:

0.477

Gnomad FIN exome

AF:

0.494

Gnomad NFE exome

AF:

0.431

Gnomad OTH exome

AF:

0.454

GnomAD4 exome

AF:

0.442

AC:

643283

AN:

1455276

Hom.:

145826

Cov.:

AF XY:

0.443

AC XY:

320731

AN XY:

724366

show subpopulations

Gnomad4 AFR exome

AF:

0.560

Gnomad4 AMR exome

AF:

0.383

Gnomad4 ASJ exome

AF:

0.400

Gnomad4 EAS exome

AF:

0.769

Gnomad4 SAS exome

AF:

0.469

Gnomad4 FIN exome

AF:

0.483

Gnomad4 NFE exome

AF:

0.425

Gnomad4 OTH exome

AF:

0.463

GnomAD4 genome

AF:

0.477

AC:

72611

AN:

152118

Hom.:

17799

Cov.:

AF XY:

0.478

AC XY:

35539

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.554

Gnomad4 AMR

AF:

0.403

Gnomad4 ASJ

AF:

0.395

Gnomad4 EAS

AF:

0.748

Gnomad4 SAS

AF:

0.475

Gnomad4 FIN

AF:

0.498

Gnomad4 NFE

AF:

0.428

Gnomad4 OTH

AF:

0.479

Alfa

AF:

0.446

Hom.:

2786

Bravo

AF:

0.477

Asia WGS

AF:

0.618

AC:

2149

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 14, 2022	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

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 -
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 60% of patients studied by a panel of primary immunodeficiencies. Number of patients: 58. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.037

DANN

Benign

0.43

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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