dbSNP rs3731043: LIG1:c.2439+575T>C (chr19-48118562-A-G) – 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.2439+575T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0608 in 109,442 control chromosomes in the GnomAD database, including 246 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 0.061 ( 246 hom., cov: 21)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LIG1
NM_000234.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.571

Publications

2 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIG1	NM_000234.3 link	c.2439+575T>C		intron_variant	Intron 25 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.2439+575T>C		intron_variant	Intron 25 of 27	1	NM_000234.3	ENSP00000263274.6		P18858-1

Frequencies

GnomAD3 genomes

AF:

0.0608

AC:

6653

AN:

109418

Hom.:

246

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0153

Gnomad AMI

AF:

0.0111

Gnomad AMR

AF:

0.0472

Gnomad ASJ

AF:

0.0566

Gnomad EAS

AF:

0.000700

Gnomad SAS

AF:

0.0205

Gnomad FIN

AF:

0.158

Gnomad MID

AF:

0.0842

Gnomad NFE

AF:

0.0845

Gnomad OTH

AF:

0.0485

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

286

Hom.:

AF XY:

0.00

AC XY:

AN XY:

156

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

232

Other (OTH)

AF:

0.00

AC:

AN:

GnomAD4 genome

AF:

0.0608

AC:

6651

AN:

109442

Hom.:

246

Cov.:

AF XY:

0.0603

AC XY:

3092

AN XY:

51238

show subpopulations

African (AFR)

AF:

0.0152

AC:

428

AN:

28098

American (AMR)

AF:

0.0472

AC:

447

AN:

9474

Ashkenazi Jewish (ASJ)

AF:

0.0566

AC:

172

AN:

3038

East Asian (EAS)

AF:

0.000701

AC:

AN:

2854

South Asian (SAS)

AF:

0.0209

AC:

AN:

3296

European-Finnish (FIN)

AF:

0.158

AC:

741

AN:

4700

Middle Eastern (MID)

AF:

0.0795

AC:

AN:

176

European-Non Finnish (NFE)

AF:

0.0844

AC:

4702

AN:

55678

Other (OTH)

AF:

0.0482

AC:

AN:

1410

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

278

557

835

1114

1392

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

222

296

370

<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:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.0

(source)

DANN

Benign

0.69

PhyloP100

-0.57

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over