Variant rs3730931 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000234.3(LIG1):c.777-21A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 1,579,302 control chromosomes in the GnomAD database, including 12,325 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.15 ( 2023 hom., cov: 31)

Exomes 𝑓: 0.12 ( 10302 hom. )

Consequence

LIG1
NM_000234.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.25

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 19-48143984-T-C is Benign according to our data. Variant chr19-48143984-T-C is described in ClinVar as [Benign]. Clinvar id is 2628268.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.251 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.777-21A>G		intron_variant		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.777-21A>G		intron_variant		1	NM_000234.3	ENSP00000263274	P4	P18858-1

Frequencies

GnomAD3 genomes

AF:

0.151

AC:

22965

AN:

151866

Hom.:

2022

Cov.:

show subpopulations

Gnomad AFR

AF:

0.255

Gnomad AMI

AF:

0.0691

Gnomad AMR

AF:

0.131

Gnomad ASJ

AF:

0.0899

Gnomad EAS

AF:

0.120

Gnomad SAS

AF:

0.0815

Gnomad FIN

AF:

0.0862

Gnomad MID

AF:

0.0828

Gnomad NFE

AF:

0.115

Gnomad OTH

AF:

0.127

GnomAD3 exomes

AF:

0.119

AC:

29971

AN:

251408

Hom.:

2055

AF XY:

0.114

AC XY:

15467

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.267

Gnomad AMR exome

AF:

0.134

Gnomad ASJ exome

AF:

0.0835

Gnomad EAS exome

AF:

0.127

Gnomad SAS exome

AF:

0.0831

Gnomad FIN exome

AF:

0.0887

Gnomad NFE exome

AF:

0.112

Gnomad OTH exome

AF:

0.108

GnomAD4 exome

AF:

0.117

AC:

166592

AN:

1427318

Hom.:

10302

Cov.:

AF XY:

0.115

AC XY:

81885

AN XY:

712344

show subpopulations

Gnomad4 AFR exome

AF:

0.264

Gnomad4 AMR exome

AF:

0.133

Gnomad4 ASJ exome

AF:

0.0855

Gnomad4 EAS exome

AF:

0.0991

Gnomad4 SAS exome

AF:

0.0824

Gnomad4 FIN exome

AF:

0.0908

Gnomad4 NFE exome

AF:

0.117

Gnomad4 OTH exome

AF:

0.120

GnomAD4 genome

AF:

0.151

AC:

22984

AN:

151984

Hom.:

2023

Cov.:

AF XY:

0.148

AC XY:

10979

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.255

Gnomad4 AMR

AF:

0.131

Gnomad4 ASJ

AF:

0.0899

Gnomad4 EAS

AF:

0.120

Gnomad4 SAS

AF:

0.0812

Gnomad4 FIN

AF:

0.0862

Gnomad4 NFE

AF:

0.115

Gnomad4 OTH

AF:

0.127

Alfa

AF:

0.137

Hom.:

553

Bravo

AF:

0.160

Asia WGS

AF:

0.120

AC:

419

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

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 24% of patients studied by a panel of primary immunodeficiencies. Number of patients: 23. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.12

DANN

Benign

0.34

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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