dbSNP rs104886467: ASB10:p.Arg39Gln (chr7-151187607-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBS2_Supporting

The NM_080871.4(ASB10):c.116G>A(p.Arg39Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000408 in 1,543,214 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

ASB10
NM_080871.4 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: -2.20

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 Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.033822984).

BS2

High AC in GnomAd4 at 16 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASB10	NM_080871.4 link	c.116G>A	p.Arg39Gln	missense_variant	Exon 1 of 6		NP_543147.2	Q8WXI3-3
ASB10	NM_001142460.1 link	c.-477G>A		upstream_gene_variant			NP_001135932.2	Q8WXI3-2A0A090N8I2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
ASB10	ENST00000377867.7 link	c.116G>A	p.Arg39Gln	missense_variant	Exon 1 of 6	2	ENSP00000367098.3	Q8WXI3-3
ASB10	ENST00000415615.1 link	n.116G>A		non_coding_transcript_exon_variant	Exon 1 of 3	4	ENSP00000410871.1	F8WB38
ASB10	ENST00000275838.5 link	c.-477G>A		upstream_gene_variant		1	ENSP00000275838.1	Q8WXI3-2

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000460

AC:

AN:

152238

Hom.:

AF XY:

0.0000124

AC XY:

AN XY:

80722

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000163

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000919

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000341

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000338

AC:

AN:

1390948

Hom.:

Cov.:

AF XY:

0.0000263

AC XY:

AN XY:

684212

show subpopulations

Gnomad4 AFR exome

AF:

0.000127

Gnomad4 AMR exome

AF:

0.000141

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000282

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000408

Gnomad4 NFE exome

AF:

0.0000289

Gnomad4 OTH exome

AF:

0.0000695

GnomAD4 genome

AF:

0.000105

AC:

AN:

152266

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000892

Hom.:

Bravo

AF:

0.000113

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

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

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.59

CADD

Benign

5.8

DANN

Benign

0.87

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.48

M_CAP

Benign

0.032

MetaRNN

Benign

0.034

MetaSVM

Benign

-1.0

PROVEAN

Benign

-0.86

REVEL

Benign

0.058

Sift

Benign

0.29

Sift4G

Benign

0.36

Polyphen

0.0

Vest4

0.076

MVP

0.055

ClinPred

0.038

GERP RS

-1.7

Splicing

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