rs20581

chr19-48119170-A-G

Variant summary

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

The NM_000234.3(LIG1):c.2406T>C(p.Asp802=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 1,581,660 control chromosomes in the GnomAD database, including 259,611 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.64 ( 32670 hom., cov: 32)

Exomes 𝑓: 0.56 ( 226941 hom. )

Consequence

LIG1
NM_000234.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.84

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 19-48119170-A-G is Benign according to our data. Variant chr19-48119170-A-G is described in ClinVar as [Benign]. Clinvar id is 403034.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.84 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.846 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.2406T>C	p.Asp802=	synonymous_variant	25/28	ENST00000263274.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIG1	ENST00000263274.12 linkuse as main transcript	c.2406T>C	p.Asp802=	synonymous_variant	25/28	1	NM_000234.3	P4	P18858-1
	ENST00000596563.5 linkuse as main transcript	n.69+670A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.640

AC:

97228

AN:

152010

Hom.:

32620

Cov.:

show subpopulations

Gnomad AFR

AF:

0.846

Gnomad AMI

AF:

0.527

Gnomad AMR

AF:

0.542

Gnomad ASJ

AF:

0.482

Gnomad EAS

AF:

0.868

Gnomad SAS

AF:

0.555

Gnomad FIN

AF:

0.583

Gnomad MID

AF:

0.563

Gnomad NFE

AF:

0.544

Gnomad OTH

AF:

0.614

GnomAD3 exomes

AF:

0.576

AC:

115798

AN:

201046

Hom.:

34721

AF XY:

0.570

AC XY:

61578

AN XY:

107956

show subpopulations

Gnomad AFR exome

AF:

0.853

Gnomad AMR exome

AF:

0.506

Gnomad ASJ exome

AF:

0.484

Gnomad EAS exome

AF:

0.878

Gnomad SAS exome

AF:

0.554

Gnomad FIN exome

AF:

0.574

Gnomad NFE exome

AF:

0.530

Gnomad OTH exome

AF:

0.557

GnomAD4 exome

AF:

0.558

AC:

797677

AN:

1429532

Hom.:

226941

Cov.:

AF XY:

0.557

AC XY:

394179

AN XY:

708144

show subpopulations

Gnomad4 AFR exome

AF:

0.861

Gnomad4 AMR exome

AF:

0.515

Gnomad4 ASJ exome

AF:

0.483

Gnomad4 EAS exome

AF:

0.866

Gnomad4 SAS exome

AF:

0.548

Gnomad4 FIN exome

AF:

0.571

Gnomad4 NFE exome

AF:

0.541

Gnomad4 OTH exome

AF:

0.584

GnomAD4 genome

AF:

0.640

AC:

97333

AN:

152128

Hom.:

32670

Cov.:

AF XY:

0.637

AC XY:

47381

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.846

Gnomad4 AMR

AF:

0.542

Gnomad4 ASJ

AF:

0.482

Gnomad4 EAS

AF:

0.868

Gnomad4 SAS

AF:

0.555

Gnomad4 FIN

AF:

0.583

Gnomad4 NFE

AF:

0.544

Gnomad4 OTH

AF:

0.615

Alfa

AF:

0.556

Hom.:

27181

Bravo

AF:

0.651

Asia WGS

AF:

0.745

AC:

2590

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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 -
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 74% of patients studied by a panel of primary immunodeficiencies. Number of patients: 71. Only high quality variants are reported. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

Cadd

Benign

0.076

Dann

Benign

0.45

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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