dbSNP rs439132: LIG1:c.-57-34A>G (chr19-48165657-T-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.-57-34A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0333 in 1,537,140 control chromosomes in the GnomAD database, including 4,454 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 0.095 ( 1645 hom., cov: 31)

Exomes 𝑓: 0.027 ( 2809 hom. )

Consequence

LIG1
NM_000234.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.08

Publications

16 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=-0.94).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIG1	NM_000234.3 link	c.-57-34A>G		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.-57-34A>G		intron_variant	Intron 1 of 27	1	NM_000234.3	ENSP00000263274.6		P18858-1

Frequencies

GnomAD3 genomes

AF:

0.0948

AC:

14382

AN:

151656

Hom.:

1645

Cov.:

show subpopulations

Gnomad AFR

AF:

0.264

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0575

Gnomad ASJ

AF:

0.0115

Gnomad EAS

AF:

0.186

Gnomad SAS

AF:

0.100

Gnomad FIN

AF:

0.0539

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00653

Gnomad OTH

AF:

0.0740

GnomAD2 exomes

AF:

0.0560

AC:

14071

AN:

251156

AF XY:

0.0525

show subpopulations

Gnomad AFR exome

AF:

0.267

Gnomad AMR exome

AF:

0.0451

Gnomad ASJ exome

AF:

0.0117

Gnomad EAS exome

AF:

0.169

Gnomad FIN exome

AF:

0.0514

Gnomad NFE exome

AF:

0.00657

Gnomad OTH exome

AF:

0.0374

GnomAD4 exome

AF:

0.0266

AC:

36785

AN:

1385366

Hom.:

2809

Cov.:

AF XY:

0.0274

AC XY:

19008

AN XY:

693430

show subpopulations

African (AFR)

AF:

0.288

AC:

9211

AN:

31954

American (AMR)

AF:

0.0466

AC:

2082

AN:

44658

Ashkenazi Jewish (ASJ)

AF:

0.0111

AC:

284

AN:

25664

East Asian (EAS)

AF:

0.203

AC:

7962

AN:

39314

South Asian (SAS)

AF:

0.0915

AC:

7750

AN:

84694

European-Finnish (FIN)

AF:

0.0466

AC:

2477

AN:

53208

Middle Eastern (MID)

AF:

0.0399

AC:

225

AN:

5640

European-Non Finnish (NFE)

AF:

0.00424

AC:

4419

AN:

1042460

Other (OTH)

AF:

0.0411

AC:

2375

AN:

57774

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

1824

3647

5471

7294

9118

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

534

1068

1602

2136

2670

<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:

0.0950

AC:

14411

AN:

151774

Hom.:

1645

Cov.:

AF XY:

0.0966

AC XY:

7166

AN XY:

74180

show subpopulations

African (AFR)

AF:

0.264

AC:

10882

AN:

41266

American (AMR)

AF:

0.0572

AC:

872

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.0115

AC:

AN:

3470

East Asian (EAS)

AF:

0.186

AC:

962

AN:

5162

South Asian (SAS)

AF:

0.0994

AC:

478

AN:

4808

European-Finnish (FIN)

AF:

0.0539

AC:

568

AN:

10538

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00653

AC:

444

AN:

67970

Other (OTH)

AF:

0.0756

AC:

159

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

532

1064

1595

2127

2659

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

296

444

592

740

<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:

0.0363

Hom.:

2112

Bravo

AF:

0.102

Asia WGS

AF:

0.148

AC:

514

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.011

(source)

DANN

Benign

0.53

PhyloP100

-2.1

PromoterAI

-0.090

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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