7-151181312-C-T

Position:

chr7-151181312-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001142459.2(ASB10):c.731G>A(p.Arg244His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000203 in 1,613,222 control chromosomes in the GnomAD database, including 1 homozygotes. 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 Benign (★).

Frequency

Genomes: 𝑓 0.00036 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 1 hom. )

Consequence

ASB10
NM_001142459.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter U:1B:1O:1

Conservation

PhyloP100: 0.317

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010939121).

BP6

Variant 7-151181312-C-T is Benign according to our data. Variant chr7-151181312-C-T is described in ClinVar as [Benign]. Clinvar id is 99963.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 55 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ASB10	NM_001142459.2 linkuse as main transcript	c.731G>A	p.Arg244His	missense_variant	3/6	ENST00000420175.3	NP_001135931.2
ASB10	NM_080871.4 linkuse as main transcript	c.686G>A	p.Arg229His	missense_variant	3/6		NP_543147.2
ASB10	NM_001142460.1 linkuse as main transcript	c.731G>A	p.Arg244His	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.731G>A	p.Arg244His	missense_variant	3/6	1	NM_001142459.2	ENSP00000391137	P4	Q8WXI3-1
ASB10	ENST00000275838.5 linkuse as main transcript	c.731G>A	p.Arg244His	missense_variant	3/5	1		ENSP00000275838		Q8WXI3-2
ASB10	ENST00000377867.7 linkuse as main transcript	c.686G>A	p.Arg229His	missense_variant	3/6	2		ENSP00000367098	A1	Q8WXI3-3

Frequencies

GnomAD3 genomes

AF:

0.000361

AC:

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000434

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00616

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000413

AC:

103

AN:

249470

Hom.:

AF XY:

0.000399

AC XY:

AN XY:

135438

show subpopulations

Gnomad AFR exome

AF:

0.000187

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00485

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000535

Gnomad OTH exome

AF:

0.000492

GnomAD4 exome

AF:

0.000186

AC:

272

AN:

1460872

Hom.:

Cov.:

AF XY:

0.000187

AC XY:

136

AN XY:

726750

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00254

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000926

Gnomad4 OTH exome

AF:

0.000861

GnomAD4 genome

AF:

0.000361

AC:

AN:

152350

Hom.:

Cov.:

AF XY:

0.000456

AC XY:

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.000433

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00617

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000959

Hom.:

Bravo

AF:

0.000370

ExAC

AF:

0.000330

AC:

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 09, 2022	- -
Uncertain significance, no assertion criteria provided	clinical testing	Department of Pathology and Laboratory Medicine, Sinai Health System	-	The ASB10 p.R244H variant was not identified in the literature but was identified in dbSNP (ID: rs104886476) and in ClinVar (classification not provided by Casey Eye Institute Glaucoma Genetics Lab). The variant was identified in control databases in 117 of 280842 chromosomes (1 homozygous) at a frequency of 0.0004166, and was observed at the highest frequency in the East Asian population in 98 of 19898 chromosomes (1 homozygous) (freq: 0.004925) (Genome Aggregation Database March 6, 2019, v2.1.1). The p.R244 residue is not conserved in mammals and computational analyses (MUT Assesor, PolyPhen-2, SIFT, MutationTaster, Revel, FATHMM, MetaLR, DANN) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (Splice AI exome) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. -

Glaucoma 1, open angle, F

Other:1

not provided, no classification provided

literature only

Casey Eye Institute Glaucoma Genetics Lab

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.045

.;.;T

Eigen

Benign

0.036

Eigen_PC

Benign

-0.10

FATHMM_MKL

Benign

0.062

LIST_S2

Uncertain

0.92

D;D;D

M_CAP

Benign

0.057

MetaRNN

Benign

0.011

T;T;T

MetaSVM

Benign

-0.65

MutationAssessor

Benign

2.0

M;.;M

MutationTaster

Benign

0.94

N;N;N;N;N

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-2.9

D;D;D

REVEL

Benign

0.21

Sift

Uncertain

0.011

D;D;D

Sift4G

Benign

0.087

T;T;T

Polyphen

0.99, 0.99

.;D;D

Vest4

0.43

MVP

0.67

MPC

0.28

ClinPred

0.096

GERP RS

3.4

Varity_R

0.10

gMVP

0.25

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