dbSNP rs4987070: LIG1:p.Asp72Val (chr19-48161400-T-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000234.3(LIG1):c.215A>T(p.Asp72Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D72E) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

LIG1
NM_000234.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.32

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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17807159).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIG1	NM_000234.3 link	c.215A>T	p.Asp72Val	missense_variant	Exon 4 of 28	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.215A>T	p.Asp72Val	missense_variant	Exon 4 of 28	1	NM_000234.3	ENSP00000263274.6		P18858-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461874

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111996

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

0.0047

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.56

D;.;.;.;.;.

Eigen

Benign

0.042

Eigen_PC

Benign

0.086

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.91

D;D;D;D;D;D

M_CAP

Benign

0.077

MetaRNN

Benign

0.18

T;T;T;T;T;T

MetaSVM

Benign

-0.78

MutationAssessor

Uncertain

2.0

M;.;.;M;.;.

PhyloP100

3.3

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-3.2

D;N;D;.;.;.

REVEL

Benign

0.18

Sift

Uncertain

0.0040

D;D;D;.;.;.

Sift4G

Uncertain

0.0070

D;T;D;D;.;.

Polyphen

0.36

B;P;.;.;.;.

Vest4

0.34

MutPred

0.14

Loss of loop (P = 0.0288);Loss of loop (P = 0.0288);.;Loss of loop (P = 0.0288);Loss of loop (P = 0.0288);Loss of loop (P = 0.0288);

MVP

0.52

MPC

0.39

ClinPred

0.70

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.13

gMVP

0.18

Mutation Taster

=78/22

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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