rs61743170

Positions:

• chr7-151181245-G-A
• chr7-151181245-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001142459.2(ASB10):​c.798C>T​(p.Ala266Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0551 in 1,613,038 control chromosomes in the GnomAD database, including 2,979 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.079 (614 hom., cov: 32)
  • Exomes 𝑓: 0.053 (2365 hom.)
• Consequence: ASB10 NM_001142459.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -5.16

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 7-151181245-G-A is Benign according to our data. Variant chr7-151181245-G-A is described in ClinVar as [Benign]. Clinvar id is 677216.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-5.16 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASB10	NM_001142459.2	c.798C>T	p.Ala266Ala	synonymous_variant	3/6	ENST00000420175.3	NP_001135931.2
ASB10	NM_080871.4	c.753C>T	p.Ala251Ala	synonymous_variant	3/6		NP_543147.2
ASB10	NM_001142460.1	c.798C>T	p.Ala266Ala	synonymous_variant	3/5		NP_001135932.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASB10	ENST00000420175.3	c.798C>T	p.Ala266Ala	synonymous_variant	3/6	1	NM_001142459.2	ENSP00000391137.2
ASB10	ENST00000275838.5	c.798C>T	p.Ala266Ala	synonymous_variant	3/5	1		ENSP00000275838.1
ASB10	ENST00000377867.7	c.753C>T	p.Ala251Ala	synonymous_variant	3/6	2		ENSP00000367098.3

Frequencies

GnomAD3 genomes AF: 0.0789 AC: 12006 AN: 152144 Hom.: 616 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0567

Gnomad ASJ AF: 0.0677

Gnomad EAS AF: 0.0801

Gnomad SAS AF: 0.0421

Gnomad FIN AF: 0.0659

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0503

Gnomad OTH AF: 0.0824

GnomAD3 exomes AF: 0.0589 AC: 14623 AN: 248462 Hom.: 544 AF XY: 0.0572 AC XY: 7724 AN XY: 135010

Gnomad AFR exome AF: 0.150

Gnomad AMR exome AF: 0.0339

Gnomad ASJ exome AF: 0.0676

Gnomad EAS exome AF: 0.0797

Gnomad SAS exome AF: 0.0402

Gnomad FIN exome AF: 0.0651

Gnomad NFE exome AF: 0.0534

Gnomad OTH exome AF: 0.0563

GnomAD4 exome AF: 0.0526 AC: 76886 AN: 1460776 Hom.: 2365 Cov.: 34 AF XY: 0.0523 AC XY: 37982 AN XY: 726728

Gnomad4 AFR exome AF: 0.151

Gnomad4 AMR exome AF: 0.0359

Gnomad4 ASJ exome AF: 0.0671

Gnomad4 EAS exome AF: 0.0705

Gnomad4 SAS exome AF: 0.0416

Gnomad4 FIN exome AF: 0.0656

Gnomad4 NFE exome AF: 0.0490

Gnomad4 OTH exome AF: 0.0626

GnomAD4 genome AF: 0.0789 AC: 12010 AN: 152262 Hom.: 614 Cov.: 32 AF XY: 0.0775 AC XY: 5767 AN XY: 74440

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.0566

Gnomad4 ASJ AF: 0.0677

Gnomad4 EAS AF: 0.0799

Gnomad4 SAS AF: 0.0423

Gnomad4 FIN AF: 0.0659

Gnomad4 NFE AF: 0.0503

Gnomad4 OTH AF: 0.0815

Alfa AF: 0.0552 Hom.: 160

Bravo AF: 0.0816

Asia WGS AF: 0.0570 AC: 196 AN: 3478

EpiCase AF: 0.0541

EpiControl AF: 0.0557

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 19, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 15, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.028
DANN	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs61743170; hg19: chr7-150878332;