rs104886474

Positions:

chr7-151181424-C-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001142459.2(ASB10):c.619G>C(p.Val207Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00195 in 1,606,730 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 7 hom. )

Consequence

ASB10
NM_001142459.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts P:1B:4O:1

Conservation

PhyloP100: 2.99

Variant links:

Genes affected

ASB10 (HGNC:17185): (ankyrin repeat and SOCS box containing 10) The protein encoded by this gene is a member of the ankyrin repeat and SOCS box-containing (ASB) family of proteins. The SOCS box serves to couple suppressor of cytokine signaling (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. [provided by RefSeq, Dec 2008]

ASB10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.025848866).

BP6

Variant 7-151181424-C-G is Benign according to our data. Variant chr7-151181424-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 50953.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 239 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ASB10	NM_001142459.2 linkuse as main transcript	c.619G>C	p.Val207Leu	missense_variant	3/6	ENST00000420175.3	NP_001135931.2
ASB10	NM_080871.4 linkuse as main transcript	c.574G>C	p.Val192Leu	missense_variant	3/6		NP_543147.2
ASB10	NM_001142460.1 linkuse as main transcript	c.619G>C	p.Val207Leu	missense_variant	3/5		NP_001135932.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASB10	ENST00000420175.3 linkuse as main transcript	c.619G>C	p.Val207Leu	missense_variant	3/6	1	NM_001142459.2	ENSP00000391137	P4	Q8WXI3-1
ASB10	ENST00000275838.5 linkuse as main transcript	c.619G>C	p.Val207Leu	missense_variant	3/5	1		ENSP00000275838		Q8WXI3-2
ASB10	ENST00000377867.7 linkuse as main transcript	c.574G>C	p.Val192Leu	missense_variant	3/6	2		ENSP00000367098	A1	Q8WXI3-3

Frequencies

GnomAD3 genomes

AF:

0.00157

AC:

239

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00307

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00131

AC:

318

AN:

243510

Hom.:

AF XY:

0.00133

AC XY:

177

AN XY:

132730

show subpopulations

Gnomad AFR exome

AF:

0.000321

Gnomad AMR exome

AF:

0.000670

Gnomad ASJ exome

AF:

0.000104

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000401

Gnomad FIN exome

AF:

0.0000467

Gnomad NFE exome

AF:

0.00244

Gnomad OTH exome

AF:

0.00200

GnomAD4 exome

AF:

0.00200

AC:

2902

AN:

1454458

Hom.:

Cov.:

AF XY:

0.00195

AC XY:

1410

AN XY:

722430

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.000674

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000280

Gnomad4 FIN exome

AF:

0.000153

Gnomad4 NFE exome

AF:

0.00243

Gnomad4 OTH exome

AF:

0.00225

GnomAD4 genome

AF:

0.00157

AC:

239

AN:

152272

Hom.:

Cov.:

AF XY:

0.00144

AC XY:

107

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00307

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00183

Hom.:

Bravo

AF:

0.00157

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00245

AC:

ExAC

AF:

0.00133

AC:

161

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Pathogenic:1Benign:4Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Sep 10, 2023	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2023	ASB10: BS1, BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Glaucoma 1, open angle, F

Pathogenic:1Other:1

Pathogenic, no assertion criteria provided	literature only	OMIM	Mar 15, 2012	- -
not provided, no classification provided	literature only	Casey Eye Institute Glaucoma Genetics Lab	-	- -

ASB10-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 10, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.039

.;.;T

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.87

D;D;D

M_CAP

Benign

0.017

MetaRNN

Benign

0.026

T;T;T

MetaSVM

Benign

-0.78

MutationAssessor

Benign

0.78

N;.;N

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-2.3

N;D;N

REVEL

Benign

0.13

Sift

Uncertain

0.0060

D;D;D

Sift4G

Uncertain

0.019

D;D;D

Polyphen

0.60, 0.90

.;P;P

Vest4

0.66

MVP

0.44

MPC

0.14

ClinPred

0.023

GERP RS

5.1

Varity_R

0.23

gMVP

0.43

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over