rs104886474

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.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

Publications

6 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=0.025848866).

BP6

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

BS2

High AC in GnomAd4 at 239 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASB10	NM_001142459.2 link	c.619G>C	p.Val207Leu	missense_variant	Exon 3 of 6	ENST00000420175.3	NP_001135931.2	Q8WXI3-1
ASB10	NM_080871.4 link	c.574G>C	p.Val192Leu	missense_variant	Exon 3 of 6		NP_543147.2	Q8WXI3-3
ASB10	NM_001142460.1 link	c.619G>C	p.Val207Leu	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.619G>C	p.Val207Leu	missense_variant	Exon 3 of 6	1	NM_001142459.2	ENSP00000391137.2	Q8WXI3-1
ASB10	ENST00000275838.5 link	c.619G>C	p.Val207Leu	missense_variant	Exon 3 of 5	1		ENSP00000275838.1	Q8WXI3-2
ASB10	ENST00000377867.7 link	c.574G>C	p.Val192Leu	missense_variant	Exon 3 of 6	2		ENSP00000367098.3	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

GnomAD2 exomes

AF:

0.00131

AC:

318

AN:

243510

AF XY:

0.00133

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 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

African (AFR)

AF:

0.000269

AC:

AN:

33398

American (AMR)

AF:

0.000674

AC:

AN:

44532

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25830

East Asian (EAS)

AF:

0.00

AC:

AN:

39562

South Asian (SAS)

AF:

0.000280

AC:

AN:

85676

European-Finnish (FIN)

AF:

0.000153

AC:

AN:

52138

Middle Eastern (MID)

AF:

0.000522

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.00243

AC:

2693

AN:

1107508

Other (OTH)

AF:

0.00225

AC:

135

AN:

60062

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

181

363

544

726

907

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

196

294

392

490

<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:

0.00157

AC:

239

AN:

152272

Hom.:

Cov.:

AF XY:

0.00144

AC XY:

107

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.000385

AC:

AN:

41542

American (AMR)

AF:

0.000458

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.000414

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00307

AC:

209

AN:

68030

Other (OTH)

AF:

0.00142

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.00183

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Aug 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ASB10: BS1, BS2 -

Aug 22, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Glaucoma 1, open angle, F

Pathogenic:1Other:1

Mar 15, 2012

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Casey Eye Institute Glaucoma Genetics Lab

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

- -

ASB10-related disorder

Benign:1

Jan 10, 2024

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

(source)

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

PhyloP100

3.0

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

Mutation Taster

=93/7

disease causing (ClinVar)

(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