Variant rs3730933 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000234.3(LIG1):c.800A>G(p.Asn267Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0021 in 1,613,956 control chromosomes in the GnomAD database, including 62 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.011 ( 39 hom., cov: 31)

Exomes 𝑓: 0.0011 ( 23 hom. )

Consequence

LIG1
NM_000234.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.68

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0048131347).

BP6

Variant 19-48143940-T-C is Benign according to our data. Variant chr19-48143940-T-C is described in ClinVar as [Benign]. Clinvar id is 1164977.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0114 (1736/152184) while in subpopulation AFR AF= 0.0385 (1597/41514). AF 95% confidence interval is 0.0369. There are 39 homozygotes in gnomad4. There are 818 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 39 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIG1	NM_000234.3 linkuse as main transcript	c.800A>G	p.Asn267Ser	missense_variant	10/28	ENST00000263274.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIG1	ENST00000263274.12 linkuse as main transcript	c.800A>G	p.Asn267Ser	missense_variant	10/28	1	NM_000234.3	P4	P18858-1

Frequencies

GnomAD3 genomes

AF:

0.0114

AC:

1730

AN:

152066

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0384

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00728

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00957

GnomAD3 exomes

AF:

0.00300

AC:

754

AN:

251496

Hom.:

AF XY:

0.00210

AC XY:

286

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.0400

Gnomad AMR exome

AF:

0.00257

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000439

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00113

AC:

1652

AN:

1461772

Hom.:

Cov.:

AF XY:

0.000968

AC XY:

704

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.0391

Gnomad4 AMR exome

AF:

0.00271

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000495

Gnomad4 OTH exome

AF:

0.00263

GnomAD4 genome

AF:

0.0114

AC:

1736

AN:

152184

Hom.:

Cov.:

AF XY:

0.0110

AC XY:

818

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.0385

Gnomad4 AMR

AF:

0.00727

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00947

Alfa

AF:

0.00322

Hom.:

Bravo

AF:

0.0136

ESP6500AA

AF:

0.0370

AC:

163

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00362

AC:

440

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.28

T;.;.;.

Eigen

Benign

-0.11

Eigen_PC

Benign

0.031

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.89

D;D;D;D

MetaRNN

Benign

0.0048

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;.;.;M

MutationTaster

Benign

0.68

D;N;N;N

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-2.4

N;N;N;.

REVEL

Benign

0.045

Sift

Benign

0.038

D;T;D;.

Sift4G

Benign

0.19

T;T;T;T

Polyphen

0.087

B;B;.;.

Vest4

0.27

MVP

0.33

MPC

0.25

ClinPred

0.023

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.10

gMVP

0.18

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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