rs20581

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000234.3(LIG1):c.2406T>C(p.Asp802Asp) 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:4

Conservation

PhyloP100: -1.84

Publications

35 publications found

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 Gene-Disease associations (from GenCC):

immunodeficiency 96
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

LIG1 links:

ENSG00000269534 (HGNC:):

ENSG00000269534 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
LIG1	NM_000234.3 link	c.2406T>C	p.Asp802Asp	synonymous_variant	Exon 25 of 28	ENST00000263274.12	NP_000225.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIG1	ENST00000263274.12 link	c.2406T>C	p.Asp802Asp	synonymous_variant	Exon 25 of 28	1	NM_000234.3	ENSP00000263274.6

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

GnomAD2 exomes

AF:

0.576

AC:

115798

AN:

201046

AF XY:

0.570

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 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

African (AFR)

AF:

0.861

AC:

27950

AN:

32448

American (AMR)

AF:

0.515

AC:

20949

AN:

40652

Ashkenazi Jewish (ASJ)

AF:

0.483

AC:

12366

AN:

25598

East Asian (EAS)

AF:

0.866

AC:

32531

AN:

37586

South Asian (SAS)

AF:

0.548

AC:

44668

AN:

81540

European-Finnish (FIN)

AF:

0.571

AC:

29239

AN:

51206

Middle Eastern (MID)

AF:

0.544

AC:

3092

AN:

5688

European-Non Finnish (NFE)

AF:

0.541

AC:

592329

AN:

1095660

Other (OTH)

AF:

0.584

AC:

34553

AN:

59154

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

17577

35155

52732

70310

87887

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17018

34036

51054

68072

85090

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.640

AC:

97333

AN:

152128

Hom.:

32670

Cov.:

AF XY:

0.637

AC XY:

47381

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.846

AC:

35135

AN:

41510

American (AMR)

AF:

0.542

AC:

8286

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.482

AC:

1673

AN:

3470

East Asian (EAS)

AF:

0.868

AC:

4482

AN:

5166

South Asian (SAS)

AF:

0.555

AC:

2672

AN:

4812

European-Finnish (FIN)

AF:

0.583

AC:

6183

AN:

10598

Middle Eastern (MID)

AF:

0.568

AC:

167

AN:

294

European-Non Finnish (NFE)

AF:

0.544

AC:

36954

AN:

67974

Other (OTH)

AF:

0.615

AC:

1301

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1699

3398

5098

6797

8496

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

778

1556

2334

3112

3890

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.567

Hom.:

36222

Bravo

AF:

0.651

Asia WGS

AF:

0.745

AC:

2590

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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 -

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.076

(source)

DANN

Benign

0.45

PhyloP100

-1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over