7-151181133-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001142459.2(ASB10):c.910C>T(p.Arg304Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00287 in 1,611,646 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R304H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0026 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0029 ( 12 hom. )

Consequence

ASB10
NM_001142459.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2O:1

Conservation

PhyloP100: 1.52

Publications

12 publications found

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 Gene-Disease associations (from GenCC):

glaucoma 1, open angle, F
Inheritance: AD, Unknown Classification: LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)

ASB10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008752853).

BP6

Variant 7-151181133-G-A is Benign according to our data. Variant chr7-151181133-G-A is described in ClinVar as Benign. ClinVar VariationId is 99966.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 401 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASB10	NM_001142459.2 link	c.910C>T	p.Arg304Cys	missense_variant	Exon 3 of 6	ENST00000420175.3	NP_001135931.2	Q8WXI3-1
ASB10	NM_080871.4 link	c.865C>T	p.Arg289Cys	missense_variant	Exon 3 of 6		NP_543147.2	Q8WXI3-3
ASB10	NM_001142460.1 link	c.910C>T	p.Arg304Cys	missense_variant	Exon 3 of 5		NP_001135932.2	Q8WXI3-2A0A090N8I2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ASB10	ENST00000420175.3 link	c.910C>T	p.Arg304Cys	missense_variant	Exon 3 of 6	1	NM_001142459.2	ENSP00000391137.2	Q8WXI3-1
ASB10	ENST00000275838.5 link	c.910C>T	p.Arg304Cys	missense_variant	Exon 3 of 5	1		ENSP00000275838.1	Q8WXI3-2
ASB10	ENST00000377867.7 link	c.865C>T	p.Arg289Cys	missense_variant	Exon 3 of 6	2		ENSP00000367098.3	Q8WXI3-3

Frequencies

GnomAD3 genomes

AF:

0.00263

AC:

401

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000772

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.00922

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00772

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00320

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00299

AC:

733

AN:

245448

AF XY:

0.00305

show subpopulations

Gnomad AFR exome

AF:

0.000702

Gnomad AMR exome

AF:

0.00180

Gnomad ASJ exome

AF:

0.0107

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00793

Gnomad NFE exome

AF:

0.00325

Gnomad OTH exome

AF:

0.00265

GnomAD4 exome

AF:

0.00290

AC:

4230

AN:

1459296

Hom.:

Cov.:

AF XY:

0.00288

AC XY:

2087

AN XY:

725776

show subpopulations

African (AFR)

AF:

0.000508

AC:

AN:

33468

American (AMR)

AF:

0.00175

AC:

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.00962

AC:

251

AN:

26090

East Asian (EAS)

AF:

0.0000757

AC:

AN:

39652

South Asian (SAS)

AF:

0.000394

AC:

AN:

86204

European-Finnish (FIN)

AF:

0.00816

AC:

424

AN:

51964

Middle Eastern (MID)

AF:

0.00383

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

0.00290

AC:

3219

AN:

1111186

Other (OTH)

AF:

0.00302

AC:

182

AN:

60304

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

276

553

829

1106

1382

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

252

378

504

630

<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

AF:

0.00263

AC:

401

AN:

152350

Hom.:

Cov.:

AF XY:

0.00282

AC XY:

210

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.000769

AC:

AN:

41588

American (AMR)

AF:

0.00189

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00922

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5180

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00772

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00320

AC:

218

AN:

68034

Other (OTH)

AF:

0.00189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

100

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

Alfa

AF:

0.00210

Hom.:

Bravo

AF:

0.00227

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.000455

AC:

ESP6500EA

AF:

0.00373

AC:

ExAC

AF:

0.00271

AC:

329

EpiCase

AF:

0.00360

EpiControl

AF:

0.00445

ClinVar

Significance: Benign

Submissions summary: Benign:2Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 11, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Glaucoma 1, open angle, F

Other:1

Casey Eye Institute Glaucoma Genetics Lab

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.35

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.023

.;.;T

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.96

D;D;D

M_CAP

Benign

0.074

MetaRNN

Benign

0.0088

T;T;T

MetaSVM

Benign

-0.72

MutationAssessor

Benign

0.76

N;.;N

PhyloP100

1.5

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.9

N;D;N

REVEL

Benign

0.23

Sift

Uncertain

0.014

D;D;D

Sift4G

Uncertain

0.027

D;D;D

Polyphen

1.0, 1.0

.;D;D

Vest4

0.47

MVP

0.63

MPC

0.31

ClinPred

0.023

GERP RS

5.3

Varity_R

0.10

gMVP

0.31

Mutation Taster

=99/1

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over