Variant chr19-48115897-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_000234.3(LIG1):c.2652G>A(p.Pro884=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0121 in 1,613,912 control chromosomes in the GnomAD database, including 157 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0095 ( 10 hom., cov: 32)

Exomes 𝑓: 0.012 ( 147 hom. )

Consequence

LIG1
NM_000234.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.49

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 19-48115897-C-T is Benign according to our data. Variant chr19-48115897-C-T is described in ClinVar as [Benign]. Clinvar id is 1169235.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.49 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIG1	NM_000234.3 linkuse as main transcript	c.2652G>A	p.Pro884=	synonymous_variant	27/28	ENST00000263274.12	NP_000225.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIG1	ENST00000263274.12 linkuse as main transcript	c.2652G>A	p.Pro884=	synonymous_variant	27/28	1	NM_000234.3	ENSP00000263274	P4	P18858-1

Frequencies

GnomAD3 genomes

AF:

0.00955

AC:

1453

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00186

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00314

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00952

Gnomad FIN

AF:

0.0204

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0151

Gnomad OTH

AF:

0.00670

GnomAD3 exomes

AF:

0.00989

AC:

2482

AN:

251040

Hom.:

AF XY:

0.0103

AC XY:

1402

AN XY:

135736

show subpopulations

Gnomad AFR exome

AF:

0.00209

Gnomad AMR exome

AF:

0.00202

Gnomad ASJ exome

AF:

0.00437

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0103

Gnomad FIN exome

AF:

0.0217

Gnomad NFE exome

AF:

0.0132

Gnomad OTH exome

AF:

0.00832

GnomAD4 exome

AF:

0.0123

AC:

18037

AN:

1461652

Hom.:

147

Cov.:

AF XY:

0.0124

AC XY:

9025

AN XY:

727126

show subpopulations

Gnomad4 AFR exome

AF:

0.00185

Gnomad4 AMR exome

AF:

0.00201

Gnomad4 ASJ exome

AF:

0.00413

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0105

Gnomad4 FIN exome

AF:

0.0219

Gnomad4 NFE exome

AF:

0.0135

Gnomad4 OTH exome

AF:

0.0107

GnomAD4 genome

AF:

0.00954

AC:

1453

AN:

152260

Hom.:

Cov.:

AF XY:

0.00931

AC XY:

693

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.00185

Gnomad4 AMR

AF:

0.00314

Gnomad4 ASJ

AF:

0.00634

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00953

Gnomad4 FIN

AF:

0.0204

Gnomad4 NFE

AF:

0.0151

Gnomad4 OTH

AF:

0.00663

Alfa

AF:

0.0119

Hom.:

Bravo

AF:

0.00745

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.0127

EpiControl

AF:

0.0109

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	LIG1: BP4, BP7, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
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

-0.64

CADD

Benign

0.27

DANN

Benign

0.62

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

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