dbSNP rs3730865: LIG1:c.244-114T>C (chr19-48157254-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_000234.3(LIG1):c.244-114T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0375 in 1,233,244 control chromosomes in the GnomAD database, including 1,036 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 0.026 ( 76 hom., cov: 31)

Exomes 𝑓: 0.039 ( 960 hom. )

Consequence

LIG1
NM_000234.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.283

Publications

3 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=-0.88).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0255 (3886/152184) while in subpopulation NFE AF = 0.0416 (2827/68002). AF 95% confidence interval is 0.0403. There are 76 homozygotes in GnomAd4. There are 1779 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 76 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIG1	NM_000234.3 link	c.244-114T>C		intron_variant	Intron 4 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.244-114T>C		intron_variant	Intron 4 of 27	1	NM_000234.3	ENSP00000263274.6		P18858-1

Frequencies

GnomAD3 genomes

AF:

0.0256

AC:

3889

AN:

152066

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00804

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.0262

Gnomad ASJ

AF:

0.0179

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0214

Gnomad FIN

AF:

0.00529

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0416

Gnomad OTH

AF:

0.0368

GnomAD4 exome

AF:

0.0392

AC:

42371

AN:

1081060

Hom.:

960

AF XY:

0.0388

AC XY:

20782

AN XY:

535190

show subpopulations

African (AFR)

AF:

0.00598

AC:

150

AN:

25068

American (AMR)

AF:

0.0209

AC:

554

AN:

26524

Ashkenazi Jewish (ASJ)

AF:

0.0183

AC:

296

AN:

16146

East Asian (EAS)

AF:

0.00

AC:

AN:

33138

South Asian (SAS)

AF:

0.0225

AC:

1264

AN:

56266

European-Finnish (FIN)

AF:

0.00669

AC:

281

AN:

42026

Middle Eastern (MID)

AF:

0.0430

AC:

130

AN:

3026

European-Non Finnish (NFE)

AF:

0.0457

AC:

38147

AN:

834314

Other (OTH)

AF:

0.0348

AC:

1549

AN:

44552

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

1873

3745

5618

7490

9363

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1452

2904

4356

5808

7260

<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:

0.0255

AC:

3886

AN:

152184

Hom.:

Cov.:

AF XY:

0.0239

AC XY:

1779

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.00802

AC:

333

AN:

41538

American (AMR)

AF:

0.0262

AC:

400

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0179

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.0212

AC:

102

AN:

4818

European-Finnish (FIN)

AF:

0.00529

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0416

AC:

2827

AN:

68002

Other (OTH)

AF:

0.0365

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

189

379

568

758

947

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

184

230

<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:

0.0292

Hom.:

Bravo

AF:

0.0270

Asia WGS

AF:

0.00606

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.97

(source)

DANN

Benign

0.79

PhyloP100

-0.28

Mutation Taster

=100/0

polymorphism

(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