Variant chr7-123616231-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001290258.2(ASB15):c.118C>G(p.Leu40Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000188 in 1,599,154 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ASB15
NM_001290258.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.228

Variant links:

Genes affected

ASB15 (HGNC:19767): (ankyrin repeat and SOCS box containing 15) This gene encodes a member of the suppressor of cytokine signaling box superfamily. The proteins in this superfamily participate in the ubiquitin-proteasome system for the degradation of proteins in the cell cycle and signal transduction pathways. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

ASB15 links:

ASB15-AS1 (HGNC:):

ASB15-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.056105733).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASB15	NM_001290258.2 linkuse as main transcript	c.118C>G	p.Leu40Val	missense_variant	5/12	ENST00000451215.6	NP_001277187.1	Q8WXK1A0A384NYV2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASB15	ENST00000451215.6 linkuse as main transcript	c.118C>G	p.Leu40Val	missense_variant	5/12	2	NM_001290258.2	ENSP00000416433.1		Q8WXK1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151866

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251114

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135766

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1447288

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

720956

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151866

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74150

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 19, 2023

The c.118C>G (p.L40V) alteration is located in exon 3 (coding exon 2) of the ASB15 gene. This alteration results from a C to G substitution at nucleotide position 118, causing the leucine (L) at amino acid position 40 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.51

CADD

Benign

5.9

DANN

Benign

0.90

DEOGEN2

Benign

0.0058

T;T;.;T;.;T

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.065

LIST_S2

Benign

0.70

.;.;T;.;T;T

M_CAP

Benign

0.0063

MetaRNN

Benign

0.056

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.87

L;L;.;L;.;L

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.27

N;N;N;N;N;N

REVEL

Benign

0.070

Sift

Benign

0.34

T;T;T;T;T;T

Sift4G

Benign

0.50

T;T;T;T;T;T

Polyphen

0.0

B;B;.;B;.;B

Vest4

0.058

MutPred

0.29

Gain of MoRF binding (P = 0.1528);Gain of MoRF binding (P = 0.1528);Gain of MoRF binding (P = 0.1528);Gain of MoRF binding (P = 0.1528);Gain of MoRF binding (P = 0.1528);Gain of MoRF binding (P = 0.1528);

MVP

0.39

MPC

0.14

ClinPred

0.019

GERP RS

0.57

Varity_R

0.048

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over