dbSNP rs274860: LIG1:c.371-396C>T (chr19-48154363-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.371-396C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0959 in 304,542 control chromosomes in the GnomAD database, including 2,658 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 0.12 ( 2068 hom., cov: 30)

Exomes 𝑓: 0.067 ( 590 hom. )

Consequence

LIG1
NM_000234.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.471

Publications

11 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:

LIG1-AS1 (HGNC:58602):

LIG1-AS1 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=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIG1	NM_000234.3 link	c.371-396C>T		intron_variant	Intron 5 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.371-396C>T		intron_variant	Intron 5 of 27	1	NM_000234.3	ENSP00000263274.6		P18858-1

Frequencies

GnomAD3 genomes

AF:

0.125

AC:

18907

AN:

151574

Hom.:

2069

Cov.:

show subpopulations

Gnomad AFR

AF:

0.294

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0853

Gnomad ASJ

AF:

0.0631

Gnomad EAS

AF:

0.190

Gnomad SAS

AF:

0.105

Gnomad FIN

AF:

0.0649

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0420

Gnomad OTH

AF:

0.105

GnomAD4 exome

AF:

0.0672

AC:

10278

AN:

152850

Hom.:

590

Cov.:

AF XY:

0.0686

AC XY:

5609

AN XY:

81776

show subpopulations

African (AFR)

AF:

0.295

AC:

1430

AN:

4848

American (AMR)

AF:

0.0698

AC:

640

AN:

9170

Ashkenazi Jewish (ASJ)

AF:

0.0621

AC:

232

AN:

3736

East Asian (EAS)

AF:

0.170

AC:

1273

AN:

7500

South Asian (SAS)

AF:

0.0908

AC:

2471

AN:

27208

European-Finnish (FIN)

AF:

0.0563

AC:

341

AN:

6058

Middle Eastern (MID)

AF:

0.108

AC:

AN:

546

European-Non Finnish (NFE)

AF:

0.0384

AC:

3306

AN:

86128

Other (OTH)

AF:

0.0687

AC:

526

AN:

7656

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

414

828

1242

1656

2070

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

204

306

408

510

<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:

0.125

AC:

18932

AN:

151692

Hom.:

2068

Cov.:

AF XY:

0.125

AC XY:

9247

AN XY:

74084

show subpopulations

African (AFR)

AF:

0.294

AC:

12148

AN:

41260

American (AMR)

AF:

0.0850

AC:

1293

AN:

15216

Ashkenazi Jewish (ASJ)

AF:

0.0631

AC:

219

AN:

3470

East Asian (EAS)

AF:

0.190

AC:

975

AN:

5144

South Asian (SAS)

AF:

0.103

AC:

497

AN:

4806

European-Finnish (FIN)

AF:

0.0649

AC:

683

AN:

10516

Middle Eastern (MID)

AF:

0.0884

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0420

AC:

2853

AN:

67972

Other (OTH)

AF:

0.106

AC:

224

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

751

1503

2254

3006

3757

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

198

396

594

792

990

<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:

0.0592

Hom.:

918

Bravo

AF:

0.133

Asia WGS

AF:

0.150

AC:

522

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

3.8

(source)

DANN

Benign

0.75

PhyloP100

0.47

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