Genetic Variant LIG1:c.1933-158C>G (chr19-48127506-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000234.3(LIG1):c.1933-158C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 687,764 control chromosomes in the GnomAD database, including 78,854 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.48 ( 17786 hom., cov: 33)

Exomes 𝑓: 0.47 ( 61068 hom. )

Consequence

LIG1
NM_000234.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.01

Publications

10 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

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.1933-158C>G		intron_variant	Intron 20 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.1933-158C>G		intron_variant	Intron 20 of 27	1	NM_000234.3	ENSP00000263274.6

Frequencies

GnomAD3 genomes

AF:

0.477

AC:

72499

AN:

151920

Hom.:

17763

Cov.:

show subpopulations

Gnomad AFR

AF:

0.554

Gnomad AMI

AF:

0.459

Gnomad AMR

AF:

0.402

Gnomad ASJ

AF:

0.394

Gnomad EAS

AF:

0.749

Gnomad SAS

AF:

0.475

Gnomad FIN

AF:

0.496

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.428

Gnomad OTH

AF:

0.478

GnomAD4 exome

AF:

0.469

AC:

251006

AN:

535726

Hom.:

61068

Cov.:

AF XY:

0.469

AC XY:

133823

AN XY:

285236

show subpopulations

African (AFR)

AF:

0.558

AC:

9064

AN:

16256

American (AMR)

AF:

0.405

AC:

12460

AN:

30776

Ashkenazi Jewish (ASJ)

AF:

0.405

AC:

6630

AN:

16364

East Asian (EAS)

AF:

0.774

AC:

26647

AN:

34432

South Asian (SAS)

AF:

0.477

AC:

27274

AN:

57194

European-Finnish (FIN)

AF:

0.486

AC:

16043

AN:

33034

Middle Eastern (MID)

AF:

0.472

AC:

1107

AN:

2344

European-Non Finnish (NFE)

AF:

0.436

AC:

137711

AN:

315864

Other (OTH)

AF:

0.478

AC:

14070

AN:

29462

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

6881

13763

20644

27526

34407

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1146

2292

3438

4584

5730

<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:

72566

AN:

152038

Hom.:

17786

Cov.:

AF XY:

0.478

AC XY:

35503

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.554

AC:

22974

AN:

41462

American (AMR)

AF:

0.402

AC:

6151

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.394

AC:

1367

AN:

3466

East Asian (EAS)

AF:

0.749

AC:

3869

AN:

5168

South Asian (SAS)

AF:

0.476

AC:

2292

AN:

4820

European-Finnish (FIN)

AF:

0.496

AC:

5246

AN:

10566

Middle Eastern (MID)

AF:

0.493

AC:

145

AN:

294

European-Non Finnish (NFE)

AF:

0.428

AC:

29095

AN:

67966

Other (OTH)

AF:

0.480

AC:

1008

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1952

3904

5856

7808

9760

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

664

1328

1992

2656

3320

<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:

0.321

Hom.:

810

Bravo

AF:

0.477

Asia WGS

AF:

0.617

AC:

2148

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.018

(source)

DANN

Benign

0.50

PhyloP100

-3.0

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

Computational scores

Splicing

Publications

Other links and lift over