rs3730933

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000234.3(LIG1):c.800A>G(p.Asn267Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0021 in 1,613,956 control chromosomes in the GnomAD database, including 62 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 39 hom., cov: 31)

Exomes 𝑓: 0.0011 ( 23 hom. )

Consequence

LIG1
NM_000234.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.68

Publications

9 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0048131347).

BP6

Variant 19-48143940-T-C is Benign according to our data. Variant chr19-48143940-T-C is described in ClinVar as Benign. ClinVar VariationId is 1164977.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0114 (1736/152184) while in subpopulation AFR AF = 0.0385 (1597/41514). AF 95% confidence interval is 0.0369. There are 39 homozygotes in GnomAd4. There are 818 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 39 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIG1	NM_000234.3 link	c.800A>G	p.Asn267Ser	missense_variant	Exon 10 of 28	ENST00000263274.12	NP_000225.1	P18858-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIG1	ENST00000263274.12 link	c.800A>G	p.Asn267Ser	missense_variant	Exon 10 of 28	1	NM_000234.3	ENSP00000263274.6		P18858-1

Frequencies

GnomAD3 genomes

AF:

0.0114

AC:

1730

AN:

152066

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0384

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00728

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00957

GnomAD2 exomes

AF:

0.00300

AC:

754

AN:

251496

AF XY:

0.00210

show subpopulations

Gnomad AFR exome

AF:

0.0400

Gnomad AMR exome

AF:

0.00257

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000439

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00113

AC:

1652

AN:

1461772

Hom.:

Cov.:

AF XY:

0.000968

AC XY:

704

AN XY:

727214

show subpopulations

African (AFR)

AF:

0.0391

AC:

1308

AN:

33436

American (AMR)

AF:

0.00271

AC:

121

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000464

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.000867

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000495

AC:

AN:

1111936

Other (OTH)

AF:

0.00263

AC:

159

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.433

Heterozygous variant carriers

176

265

353

441

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

192

240

<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:

0.0114

AC:

1736

AN:

152184

Hom.:

Cov.:

AF XY:

0.0110

AC XY:

818

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.0385

AC:

1597

AN:

41514

American (AMR)

AF:

0.00727

AC:

111

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.000208

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68018

Other (OTH)

AF:

0.00947

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

168

251

335

419

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00580

Hom.:

Bravo

AF:

0.0136

ESP6500AA

AF:

0.0370

AC:

163

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00362

AC:

440

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.28

T;.;.;.

Eigen

Benign

-0.11

Eigen_PC

Benign

0.031

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.89

D;D;D;D

MetaRNN

Benign

0.0048

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;.;.;M

PhyloP100

3.7

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-2.4

N;N;N;.

REVEL

Benign

0.045

Sift

Benign

0.038

D;T;D;.

Sift4G

Benign

0.19

T;T;T;T

Polyphen

0.087

B;B;.;.

Vest4

0.27

MVP

0.33

MPC

0.25

ClinPred

0.023

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.10

gMVP

0.18

Mutation Taster

=84/16

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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