chr19-48131062-T-A

Variant names:

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.1821+14A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 1,607,394 control chromosomes in the GnomAD database, including 163,625 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 17799 hom., cov: 33)

Exomes 𝑓: 0.44 ( 145826 hom. )

Consequence

LIG1
NM_000234.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.844

Publications

9 publications found

Variant links:

COSMIC-nc: COSV104551260

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=-0.84).

BP6

Variant 19-48131062-T-A is Benign according to our data. Variant chr19-48131062-T-A is described in ClinVar as Benign. ClinVar VariationId is 403035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIG1	NM_000234.3 link	c.1821+14A>T		intron_variant	Intron 19 of 27	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.1821+14A>T		intron_variant	Intron 19 of 27	1	NM_000234.3	ENSP00000263274.6		P18858-1

Frequencies

GnomAD3 genomes

AF:

0.477

AC:

72544

AN:

152000

Hom.:

17776

Cov.:

show subpopulations

Gnomad AFR

AF:

0.554

Gnomad AMI

AF:

0.459

Gnomad AMR

AF:

0.402

Gnomad ASJ

AF:

0.395

Gnomad EAS

AF:

0.748

Gnomad SAS

AF:

0.474

Gnomad FIN

AF:

0.498

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.428

Gnomad OTH

AF:

0.478

GnomAD2 exomes

AF:

0.466

AC:

116885

AN:

250854

AF XY:

0.467

show subpopulations

Gnomad AFR exome

AF:

0.554

Gnomad AMR exome

AF:

0.376

Gnomad ASJ exome

AF:

0.406

Gnomad EAS exome

AF:

0.755

Gnomad FIN exome

AF:

0.494

Gnomad NFE exome

AF:

0.431

Gnomad OTH exome

AF:

0.454

GnomAD4 exome

AF:

0.442

AC:

643283

AN:

1455276

Hom.:

145826

Cov.:

AF XY:

0.443

AC XY:

320731

AN XY:

724366

show subpopulations

African (AFR)

AF:

0.560

AC:

18699

AN:

33362

American (AMR)

AF:

0.383

AC:

17098

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.400

AC:

10439

AN:

26102

East Asian (EAS)

AF:

0.769

AC:

30506

AN:

39666

South Asian (SAS)

AF:

0.469

AC:

40373

AN:

86122

European-Finnish (FIN)

AF:

0.483

AC:

25732

AN:

53304

Middle Eastern (MID)

AF:

0.467

AC:

2689

AN:

5754

European-Non Finnish (NFE)

AF:

0.425

AC:

469888

AN:

1106066

Other (OTH)

AF:

0.463

AC:

27859

AN:

60200

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

18278

36556

54833

73111

91389

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14474

28948

43422

57896

72370

<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:

0.477

AC:

72611

AN:

152118

Hom.:

17799

Cov.:

AF XY:

0.478

AC XY:

35539

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.554

AC:

22994

AN:

41508

American (AMR)

AF:

0.403

AC:

6156

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.395

AC:

1369

AN:

3470

East Asian (EAS)

AF:

0.748

AC:

3858

AN:

5156

South Asian (SAS)

AF:

0.475

AC:

2293

AN:

4826

European-Finnish (FIN)

AF:

0.498

AC:

5271

AN:

10582

Middle Eastern (MID)

AF:

0.493

AC:

145

AN:

294

European-Non Finnish (NFE)

AF:

0.428

AC:

29095

AN:

67972

Other (OTH)

AF:

0.479

AC:

1013

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1981

3962

5943

7924

9905

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

662

1324

1986

2648

3310

<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:

0.446

Hom.:

2786

Bravo

AF:

0.477

Asia WGS

AF:

0.618

AC:

2149

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Apr 14, 2022

GeneDx

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

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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 60% of patients studied by a panel of primary immunodeficiencies. Number of patients: 58. 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 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.037

(source)

DANN

Benign

0.43

PhyloP100

-0.84

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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