Variant 7-95495860-A-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_016116.3(ASB4):c.290A>G(p.His97Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000229 in 1,613,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

ASB4
NM_016116.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.51

Variant links:

Genes affected

ASB4 (HGNC:16009): (ankyrin repeat and SOCS box containing 4) The protein encoded by this gene is a member of the ankyrin repeat and SOCS box-containing (ASB) family of proteins. They contain ankyrin repeat sequence and SOCS box domain. The SOCS box serves to couple suppressor of cytokine signalling (SOCS) proteins and their binding partners with the elongin B and C complex, possibly targeting them for degradation. Multiple alternatively spliced transcript variants have been described for this gene but some of the full length sequences are not known. [provided by RefSeq, Jul 2008]

ASB4 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=0.060289383).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ASB4	NM_016116.3 linkuse as main transcript	c.290A>G	p.His97Arg	missense_variant	2/5	ENST00000325885.6
ASB4	NM_145872.3 linkuse as main transcript	c.290A>G	p.His97Arg	missense_variant	2/3
ASB4	XM_017012303.2 linkuse as main transcript	c.290A>G	p.His97Arg	missense_variant	2/5
ASB4	XM_047420471.1 linkuse as main transcript	c.110A>G	p.His37Arg	missense_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASB4	ENST00000325885.6 linkuse as main transcript	c.290A>G	p.His97Arg	missense_variant	2/5	1	NM_016116.3	P1	Q9Y574-1
ASB4	ENST00000428113.5 linkuse as main transcript	c.290A>G	p.His97Arg	missense_variant	2/3	1			Q9Y574-2
ASB4	ENST00000257621.4 linkuse as main transcript	n.260A>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

151934

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:

0.000772

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000835

AC:

AN:

251384

Hom.:

AF XY:

0.0000810

AC XY:

AN XY:

135858

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00114

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:

0.0000212

AC:

AN:

1461862

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000781

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:

0.0000395

AC:

AN:

152052

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000967

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000378

ExAC

AF:

0.0000741

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Benign

0.38

Eigen

Benign

-0.077

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.81

T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.060

T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.3

L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.65

PROVEAN

Benign

0.13

N;N

REVEL

Benign

0.17

Sift

Benign

1.0

T;T

Sift4G

Benign

0.30

T;T

Polyphen

0.0040

.;B

Vest4

0.46

MutPred

0.49

Loss of catalytic residue at N98 (P = 0.1545);Loss of catalytic residue at N98 (P = 0.1545);

MVP

0.76

MPC

0.070

ClinPred

0.049

GERP RS

5.3

Varity_R

0.12

gMVP

0.62

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over