7-151176649-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001142459.2(ASB10):c.1132C>T(p.Arg378Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.001 in 1,551,398 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0011 (3 hom., cov: 33)
  • Exomes 𝑓: 0.00099 (14 hom.)
• Consequence: ASB10 NM_001142459.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.50

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=0.008231372).
• BP6: Variant 7-151176649-G-A is Benign according to our data. Variant chr7-151176649-G-A is described in ClinVar as [Benign]. Clinvar id is 728668.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00112 (171/152254) while in subpopulation EAS AF= 0.0286 (148/5170). AF 95% confidence interval is 0.0249. There are 3 homozygotes in gnomad4. There are 96 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 171 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASB10	NM_001142459.2	c.1132C>T	p.Arg378Trp	missense_variant	4/6	ENST00000420175.3
ASB10	NM_080871.4	c.1087C>T	p.Arg363Trp	missense_variant	4/6
ASB10	NM_001142460.1	c.1105-352C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASB10	ENST00000420175.3	c.1132C>T	p.Arg378Trp	missense_variant	4/6	1	NM_001142459.2	P4
ASB10	ENST00000275838.5	c.1105-352C>T		intron_variant		1
ASB10	ENST00000377867.7	c.1087C>T	p.Arg363Trp	missense_variant	4/6	2		A1

Frequencies

GnomAD3 genomes AF: 0.00112 AC: 171 AN: 152136 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0286

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00239 AC: 376 AN: 157036 Hom.: 6 AF XY: 0.00232 AC XY: 193 AN XY: 83140

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000405

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0335

Gnomad SAS exome AF: 0.000220

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000328

Gnomad OTH exome AF: 0.000677

GnomAD4 exome AF: 0.000990 AC: 1385 AN: 1399144 Hom.: 14 Cov.: 32 AF XY: 0.000987 AC XY: 681 AN XY: 690020

Gnomad4 AFR exome AF: 0.000222

Gnomad4 AMR exome AF: 0.0000280

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0350

Gnomad4 SAS exome AF: 0.000593

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000139

Gnomad4 OTH exome AF: 0.00107

GnomAD4 genome AF: 0.00112 AC: 171 AN: 152254 Hom.: 3 Cov.: 33 AF XY: 0.00129 AC XY: 96 AN XY: 74434

Gnomad4 AFR AF: 0.000241

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0286

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000172 Hom.: 0

Bravo AF: 0.00135

ExAC AF: 0.000742 AC: 20

Asia WGS AF: 0.00693 AC: 24 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Nov 14, 2021

- -

ASB10-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 28, 2019

This variant is classified as 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	Benign	0.16
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Uncertain	-0.080
Cadd	Benign	23
Dann	Uncertain	1.0
Eigen	Benign	-0.032
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.70	D
LIST_S2	Uncertain	0.94	D;D
MetaRNN	Benign	0.0082	T;T
MetaSVM	Benign	-0.52	T
MutationTaster	Benign	0.97	D;D;D;D;D
PrimateAI	Benign	0.36	T
PROVEAN	Pathogenic	-4.5	D;D
REVEL	Uncertain	0.49
Sift	Uncertain	0.0050	D;D
Sift4G	Uncertain	0.0060	D;D
Polyphen		1.0	D;D
Vest4		0.58
MVP		0.73
MPC		0.27
ClinPred		0.13	T
GERP RS		1.0
Varity_R		0.35
gMVP		0.55

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: rs61628535; hg19: chr7-150873736; COSMIC: COSV51999124; COSMIC: COSV51999124;