rs3730849

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000234.3(LIG1):c.17+12C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 1,596,792 control chromosomes in the GnomAD database, including 111,129 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 8109 hom., cov: 31)

Exomes 𝑓: 0.37 ( 103020 hom. )

Consequence

LIG1
NM_000234.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.22

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 (BayesDel_noAF=-0.9).

BP6

Variant 19-48165538-G-A is Benign according to our data. Variant chr19-48165538-G-A is described in ClinVar as Benign. ClinVar VariationId is 403038.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIG1	NM_000234.3 link	c.17+12C>T		intron_variant	Intron 2 of 27	ENST00000263274.12	NP_000225.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIG1	ENST00000263274.12 link	c.17+12C>T		intron_variant	Intron 2 of 27	1	NM_000234.3	ENSP00000263274.6

Frequencies

GnomAD3 genomes

AF:

0.302

AC:

45850

AN:

151714

Hom.:

8106

Cov.:

show subpopulations

Gnomad AFR

AF:

0.115

Gnomad AMI

AF:

0.321

Gnomad AMR

AF:

0.290

Gnomad ASJ

AF:

0.316

Gnomad EAS

AF:

0.548

Gnomad SAS

AF:

0.315

Gnomad FIN

AF:

0.431

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.377

Gnomad OTH

AF:

0.330

GnomAD2 exomes

AF:

0.359

AC:

90308

AN:

251440

AF XY:

0.363

show subpopulations

Gnomad AFR exome

AF:

0.108

Gnomad AMR exome

AF:

0.294

Gnomad ASJ exome

AF:

0.330

Gnomad EAS exome

AF:

0.574

Gnomad FIN exome

AF:

0.426

Gnomad NFE exome

AF:

0.381

Gnomad OTH exome

AF:

0.359

GnomAD4 exome

AF:

0.371

AC:

535969

AN:

1444960

Hom.:

103020

Cov.:

AF XY:

0.370

AC XY:

266516

AN XY:

719868

show subpopulations

African (AFR)

AF:

0.101

AC:

3354

AN:

33216

American (AMR)

AF:

0.294

AC:

13157

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.328

AC:

8544

AN:

26058

East Asian (EAS)

AF:

0.558

AC:

22115

AN:

39606

South Asian (SAS)

AF:

0.311

AC:

26755

AN:

85936

European-Finnish (FIN)

AF:

0.419

AC:

22395

AN:

53404

Middle Eastern (MID)

AF:

0.300

AC:

1726

AN:

5746

European-Non Finnish (NFE)

AF:

0.380

AC:

416138

AN:

1096436

Other (OTH)

AF:

0.364

AC:

21785

AN:

59864

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

14735

29471

44206

58942

73677

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12904

25808

38712

51616

64520

<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:

0.302

AC:

45867

AN:

151832

Hom.:

8109

Cov.:

AF XY:

0.305

AC XY:

22647

AN XY:

74164

show subpopulations

African (AFR)

AF:

0.115

AC:

4770

AN:

41428

American (AMR)

AF:

0.290

AC:

4424

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.316

AC:

1095

AN:

3468

East Asian (EAS)

AF:

0.548

AC:

2829

AN:

5160

South Asian (SAS)

AF:

0.316

AC:

1524

AN:

4822

European-Finnish (FIN)

AF:

0.431

AC:

4519

AN:

10480

Middle Eastern (MID)

AF:

0.296

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.377

AC:

25630

AN:

67922

Other (OTH)

AF:

0.330

AC:

696

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1552

3104

4656

6208

7760

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

472

944

1416

1888

2360

<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:

0.334

Hom.:

2083

Bravo

AF:

0.287

Asia WGS

AF:

0.435

AC:

1510

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

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 57% of patients studied by a panel of primary immunodeficiencies. Number of patients: 55. Only high quality variants are reported. -

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 -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 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

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.066

(source)

DANN

Benign

0.57

PhyloP100

-2.2

PromoterAI

-0.074

Neutral

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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