Genetic Variant LIG1:c.-58+40C>T (chr19-48170201-G-A) – 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.-58+40C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 454,550 control chromosomes in the GnomAD database, including 28,553 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 0.30 ( 8123 hom., cov: 31)

Exomes 𝑓: 0.36 ( 20430 hom. )

Consequence

LIG1
NM_000234.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.12

Publications

4 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIG1	NM_000234.3 link	c.-58+40C>T		intron_variant	Intron 1 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.-58+40C>T		intron_variant	Intron 1 of 27	1	NM_000234.3	ENSP00000263274.6		P18858-1

Frequencies

GnomAD3 genomes

AF:

0.304

AC:

46058

AN:

151728

Hom.:

8120

Cov.:

show subpopulations

Gnomad AFR

AF:

0.121

Gnomad AMI

AF:

0.322

Gnomad AMR

AF:

0.290

Gnomad ASJ

AF:

0.316

Gnomad EAS

AF:

0.547

Gnomad SAS

AF:

0.315

Gnomad FIN

AF:

0.432

Gnomad MID

AF:

0.287

Gnomad NFE

AF:

0.377

Gnomad OTH

AF:

0.330

GnomAD2 exomes

AF:

0.356

AC:

45304

AN:

127110

AF XY:

0.357

show subpopulations

Gnomad AFR exome

AF:

0.114

Gnomad AMR exome

AF:

0.299

Gnomad ASJ exome

AF:

0.332

Gnomad EAS exome

AF:

0.577

Gnomad FIN exome

AF:

0.425

Gnomad NFE exome

AF:

0.383

Gnomad OTH exome

AF:

0.356

GnomAD4 exome

AF:

0.359

AC:

108642

AN:

302704

Hom.:

20430

Cov.:

AF XY:

0.357

AC XY:

61525

AN XY:

172482

show subpopulations

African (AFR)

AF:

0.126

AC:

1056

AN:

8380

American (AMR)

AF:

0.297

AC:

8087

AN:

27228

Ashkenazi Jewish (ASJ)

AF:

0.328

AC:

3522

AN:

10752

East Asian (EAS)

AF:

0.575

AC:

5222

AN:

9082

South Asian (SAS)

AF:

0.308

AC:

18401

AN:

59666

European-Finnish (FIN)

AF:

0.417

AC:

5147

AN:

12352

Middle Eastern (MID)

AF:

0.301

AC:

833

AN:

2772

European-Non Finnish (NFE)

AF:

0.386

AC:

61106

AN:

158302

Other (OTH)

AF:

0.372

AC:

5268

AN:

14170

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

4270

8539

12809

17078

21348

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

356

712

1068

1424

1780

<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:

0.303

AC:

46074

AN:

151846

Hom.:

8123

Cov.:

AF XY:

0.307

AC XY:

22765

AN XY:

74176

show subpopulations

African (AFR)

AF:

0.121

AC:

5008

AN:

41486

American (AMR)

AF:

0.291

AC:

4437

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.316

AC:

1096

AN:

3470

East Asian (EAS)

AF:

0.547

AC:

2770

AN:

5066

South Asian (SAS)

AF:

0.316

AC:

1525

AN:

4822

European-Finnish (FIN)

AF:

0.432

AC:

4547

AN:

10520

Middle Eastern (MID)

AF:

0.291

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.377

AC:

25615

AN:

67896

Other (OTH)

AF:

0.331

AC:

699

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

1501

3002

4503

6004

7505

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

474

948

1422

1896

2370

<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:

0.332

Hom.:

1743

Bravo

AF:

0.289

Asia WGS

AF:

0.435

AC:

1511

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

2.0

(source)

DANN

Benign

0.95

PhyloP100

-1.1

PromoterAI

0.018

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

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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