rs3800791

Positions:

• chr7-151176159-G-A
• chr7-151176159-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001142459.2(ASB10):​c.1357C>T​(p.Arg453Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00967 in 1,611,814 control chromosomes in the GnomAD database, including 648 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.019 (94 hom., cov: 33)
  • Exomes 𝑓: 0.0087 (554 hom.)
• Consequence: ASB10 NM_001142459.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.474

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016953051).
• BP6: Variant 7-151176159-G-A is Benign according to our data. Variant chr7-151176159-G-A is described in ClinVar as [Benign]. Clinvar id is 1233189.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASB10	NM_001142459.2	c.1357C>T	p.Arg453Cys	missense_variant	5/6	ENST00000420175.3	NP_001135931.2
ASB10	NM_080871.4	c.1312C>T	p.Arg438Cys	missense_variant	5/6		NP_543147.2
ASB10	NM_001142460.1	c.1243C>T	p.Arg415Cys	missense_variant	4/5		NP_001135932.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASB10	ENST00000420175.3	c.1357C>T	p.Arg453Cys	missense_variant	5/6	1	NM_001142459.2	ENSP00000391137.2
ASB10	ENST00000275838.5	c.1243C>T	p.Arg415Cys	missense_variant	4/5	1		ENSP00000275838.1
ASB10	ENST00000377867.7	c.1312C>T	p.Arg438Cys	missense_variant	5/6	2		ENSP00000367098.3

Frequencies

GnomAD3 genomes AF: 0.0188 AC: 2861 AN: 152164 Hom.: 92 Cov.: 33

Gnomad AFR AF: 0.0263

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0171

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.0253

Gnomad FIN AF: 0.0517

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00144

Gnomad OTH AF: 0.0124

GnomAD3 exomes AF: 0.0229 AC: 5630 AN: 245418 Hom.: 248 AF XY: 0.0213 AC XY: 2856 AN XY: 133820

Gnomad AFR exome AF: 0.0286

Gnomad AMR exome AF: 0.0236

Gnomad ASJ exome AF: 0.000303

Gnomad EAS exome AF: 0.137

Gnomad SAS exome AF: 0.0181

Gnomad FIN exome AF: 0.0510

Gnomad NFE exome AF: 0.00146

Gnomad OTH exome AF: 0.0146

GnomAD4 exome AF: 0.00872 AC: 12720 AN: 1459532 Hom.: 554 Cov.: 31 AF XY: 0.00884 AC XY: 6418 AN XY: 726082

Gnomad4 AFR exome AF: 0.0273

Gnomad4 AMR exome AF: 0.0213

Gnomad4 ASJ exome AF: 0.0000766

Gnomad4 EAS exome AF: 0.131

Gnomad4 SAS exome AF: 0.0188

Gnomad4 FIN exome AF: 0.0461

Gnomad4 NFE exome AF: 0.000662

Gnomad4 OTH exome AF: 0.0142

GnomAD4 genome AF: 0.0189 AC: 2873 AN: 152282 Hom.: 94 Cov.: 33 AF XY: 0.0221 AC XY: 1646 AN XY: 74460

Gnomad4 AFR AF: 0.0264

Gnomad4 AMR AF: 0.0170

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.0261

Gnomad4 FIN AF: 0.0517

Gnomad4 NFE AF: 0.00144

Gnomad4 OTH AF: 0.0132

Alfa AF: 0.00403 Hom.: 48

Bravo AF: 0.0190

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.00104 AC: 4

ESP6500AA AF: 0.0233 AC: 102

ESP6500EA AF: 0.00187 AC: 16

ExAC AF: 0.0215 AC: 2599

Asia WGS AF: 0.0810 AC: 284 AN: 3478

EpiCase AF: 0.000545

EpiControl AF: 0.000652

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	Jul 31, 2018	This variant is associated with the following publications: (PMID: 26713451) -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 02, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.014	.;.;T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.084	T;T;T
MetaRNN	Benign	0.0017	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	.;.;L
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.26	N;N;N
REVEL	Benign	0.055
Sift	Benign	0.12	T;T;T
Sift4G	Benign	0.10	T;T;T
Polyphen		0.0010, 0.0050	.;B;B
Vest4		0.15
MPC		0.063
ClinPred		0.0032	T
GERP RS		1.7
Varity_R		0.079
gMVP		0.59

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

Other links and lift over

dbSNP: rs3800791; hg19: chr7-150873246; COSMIC: COSV51994690; COSMIC: COSV51994690;