Variant rs3731007 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.2005-29C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0807 in 1,608,704 control chromosomes in the GnomAD database, including 9,200 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.15 ( 2817 hom., cov: 31)

Exomes 𝑓: 0.073 ( 6383 hom. )

Consequence

LIG1
NM_000234.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.436

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 2 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 19-48123347-G-A is Benign according to our data. Variant chr19-48123347-G-A is described in ClinVar as [Benign]. Clinvar id is 2688333.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.333 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.2005-29C>T		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.2005-29C>T		intron_variant		1	NM_000234.3	ENSP00000263274	P4	P18858-1
	ENST00000596563.5 linkuse as main transcript	n.176+2088G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.149

AC:

22698

AN:

152008

Hom.:

2818

Cov.:

show subpopulations

Gnomad AFR

AF:

0.338

Gnomad AMI

AF:

0.149

Gnomad AMR

AF:

0.109

Gnomad ASJ

AF:

0.0884

Gnomad EAS

AF:

0.194

Gnomad SAS

AF:

0.147

Gnomad FIN

AF:

0.0665

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.0568

Gnomad OTH

AF:

0.132

GnomAD3 exomes

AF:

0.103

AC:

25379

AN:

245830

Hom.:

2034

AF XY:

0.101

AC XY:

13518

AN XY:

133598

show subpopulations

Gnomad AFR exome

AF:

0.340

Gnomad AMR exome

AF:

0.0824

Gnomad ASJ exome

AF:

0.0871

Gnomad EAS exome

AF:

0.175

Gnomad SAS exome

AF:

0.150

Gnomad FIN exome

AF:

0.0712

Gnomad NFE exome

AF:

0.0586

Gnomad OTH exome

AF:

0.103

GnomAD4 exome

AF:

0.0735

AC:

107037

AN:

1456578

Hom.:

6383

Cov.:

AF XY:

0.0751

AC XY:

54414

AN XY:

724842

show subpopulations

Gnomad4 AFR exome

AF:

0.357

Gnomad4 AMR exome

AF:

0.0880

Gnomad4 ASJ exome

AF:

0.0852

Gnomad4 EAS exome

AF:

0.202

Gnomad4 SAS exome

AF:

0.147

Gnomad4 FIN exome

AF:

0.0671

Gnomad4 NFE exome

AF:

0.0524

Gnomad4 OTH exome

AF:

0.0963

GnomAD4 genome

AF:

0.149

AC:

22713

AN:

152126

Hom.:

2817

Cov.:

AF XY:

0.148

AC XY:

11019

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.338

Gnomad4 AMR

AF:

0.109

Gnomad4 ASJ

AF:

0.0884

Gnomad4 EAS

AF:

0.194

Gnomad4 SAS

AF:

0.146

Gnomad4 FIN

AF:

0.0665

Gnomad4 NFE

AF:

0.0568

Gnomad4 OTH

AF:

0.133

Alfa

AF:

0.105

Hom.:

481

Bravo

AF:

0.160

Asia WGS

AF:

0.166

AC:

578

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

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 21% of patients studied by a panel of primary immunodeficiencies. Number of patients: 20. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.2

DANN

Benign

0.64

BranchPoint Hunter

2.0

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