Variant rs13436 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000234.3(LIG1):c.2442G>C(p.Ala814=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 1,611,088 control chromosomes in the GnomAD database, including 162,858 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A814A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.47 ( 17579 hom., cov: 34)

Exomes 𝑓: 0.44 ( 145279 hom. )

Consequence

LIG1
NM_000234.3 splice_region, synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.688

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 19-48117779-C-G is Benign according to our data. Variant chr19-48117779-C-G is described in ClinVar as [Benign]. Clinvar id is 403033.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.688 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIG1	NM_000234.3 linkuse as main transcript	c.2442G>C	p.Ala814=	splice_region_variant, synonymous_variant	26/28	ENST00000263274.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIG1	ENST00000263274.12 linkuse as main transcript	c.2442G>C	p.Ala814=	splice_region_variant, synonymous_variant	26/28	1	NM_000234.3	P4	P18858-1

Frequencies

GnomAD3 genomes

AF:

0.475

AC:

72135

AN:

152012

Hom.:

17560

Cov.:

show subpopulations

Gnomad AFR

AF:

0.544

Gnomad AMI

AF:

0.461

Gnomad AMR

AF:

0.402

Gnomad ASJ

AF:

0.393

Gnomad EAS

AF:

0.750

Gnomad SAS

AF:

0.473

Gnomad FIN

AF:

0.497

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.428

Gnomad OTH

AF:

0.479

GnomAD3 exomes

AF:

0.463

AC:

113343

AN:

244628

Hom.:

27359

AF XY:

0.464

AC XY:

61256

AN XY:

132114

show subpopulations

Gnomad AFR exome

AF:

0.541

Gnomad AMR exome

AF:

0.374

Gnomad ASJ exome

AF:

0.404

Gnomad EAS exome

AF:

0.754

Gnomad SAS exome

AF:

0.476

Gnomad FIN exome

AF:

0.492

Gnomad NFE exome

AF:

0.429

Gnomad OTH exome

AF:

0.453

GnomAD4 exome

AF:

0.441

AC:

643367

AN:

1458958

Hom.:

145279

Cov.:

AF XY:

0.442

AC XY:

320384

AN XY:

725416

show subpopulations

Gnomad4 AFR exome

AF:

0.547

Gnomad4 AMR exome

AF:

0.381

Gnomad4 ASJ exome

AF:

0.398

Gnomad4 EAS exome

AF:

0.769

Gnomad4 SAS exome

AF:

0.468

Gnomad4 FIN exome

AF:

0.483

Gnomad4 NFE exome

AF:

0.424

Gnomad4 OTH exome

AF:

0.461

GnomAD4 genome

AF:

0.475

AC:

72196

AN:

152130

Hom.:

17579

Cov.:

AF XY:

0.475

AC XY:

35353

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.544

Gnomad4 AMR

AF:

0.402

Gnomad4 ASJ

AF:

0.393

Gnomad4 EAS

AF:

0.750

Gnomad4 SAS

AF:

0.474

Gnomad4 FIN

AF:

0.497

Gnomad4 NFE

AF:

0.428

Gnomad4 OTH

AF:

0.481

Alfa

AF:

0.400

Hom.:

3715

Bravo

AF:

0.474

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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. -
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 -

not provided

Benign:2

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

8.5

DANN

Benign

0.78

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