7-151176667-G-A

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.1114C>T(p.Arg372Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0545 in 1,550,106 control chromosomes in the GnomAD database, including 2,567 homozygotes. In-silico tool predicts 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 0.068 (402 hom., cov: 32)
  • Exomes 𝑓: 0.053 (2165 hom.)
• Consequence: ASB10 NM_001142459.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.10

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=0.003540486).
• BP6: Variant 7-151176667-G-A is Benign according to our data. Variant chr7-151176667-G-A is described in ClinVar as [Benign]. Clinvar id is 677160.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASB10	NM_001142459.2	c.1114C>T	p.Arg372Cys	missense_variant	4/6	ENST00000420175.3
ASB10	NM_080871.4	c.1069C>T	p.Arg357Cys	missense_variant	4/6
ASB10	NM_001142460.1	c.1105-370C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASB10	ENST00000420175.3	c.1114C>T	p.Arg372Cys	missense_variant	4/6	1	NM_001142459.2	P4
ASB10	ENST00000275838.5	c.1105-370C>T		intron_variant		1
ASB10	ENST00000377867.7	c.1069C>T	p.Arg357Cys	missense_variant	4/6	2		A1

Frequencies

GnomAD3 genomes AF: 0.0675 AC: 10272 AN: 152074 Hom.: 402 Cov.: 32

Gnomad AFR AF: 0.0976

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0490

Gnomad ASJ AF: 0.0677

Gnomad EAS AF: 0.0848

Gnomad SAS AF: 0.0381

Gnomad FIN AF: 0.0789

Gnomad MID AF: 0.0545

Gnomad NFE AF: 0.0530

Gnomad OTH AF: 0.0745

GnomAD3 exomes AF: 0.0553 AC: 8685 AN: 156914 Hom.: 289 AF XY: 0.0545 AC XY: 4529 AN XY: 83044

Gnomad AFR exome AF: 0.0971

Gnomad AMR exome AF: 0.0311

Gnomad ASJ exome AF: 0.0653

Gnomad EAS exome AF: 0.0857

Gnomad SAS exome AF: 0.0331

Gnomad FIN exome AF: 0.0776

Gnomad NFE exome AF: 0.0549

Gnomad OTH exome AF: 0.0574

GnomAD4 exome AF: 0.0531 AC: 74187 AN: 1397912 Hom.: 2165 Cov.: 31 AF XY: 0.0528 AC XY: 36388 AN XY: 689398

Gnomad4 AFR exome AF: 0.0953

Gnomad4 AMR exome AF: 0.0332

Gnomad4 ASJ exome AF: 0.0668

Gnomad4 EAS exome AF: 0.0744

Gnomad4 SAS exome AF: 0.0355

Gnomad4 FIN exome AF: 0.0776

Gnomad4 NFE exome AF: 0.0512

Gnomad4 OTH exome AF: 0.0603

GnomAD4 genome AF: 0.0675 AC: 10276 AN: 152194 Hom.: 402 Cov.: 32 AF XY: 0.0680 AC XY: 5059 AN XY: 74396

Gnomad4 AFR AF: 0.0976

Gnomad4 AMR AF: 0.0490

Gnomad4 ASJ AF: 0.0677

Gnomad4 EAS AF: 0.0846

Gnomad4 SAS AF: 0.0381

Gnomad4 FIN AF: 0.0789

Gnomad4 NFE AF: 0.0530

Gnomad4 OTH AF: 0.0737

Alfa AF: 0.0565 Hom.: 371

Bravo AF: 0.0670

TwinsUK AF: 0.0467 AC: 173

ALSPAC AF: 0.0537 AC: 207

ExAC AF: 0.0498 AC: 1342

Asia WGS AF: 0.0550 AC: 190 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 15, 2024	- -
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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.16
Cadd	Pathogenic	28
Dann	Pathogenic	1.0
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Benign	0.68	D
LIST_S2	Uncertain	0.88	D;D
MetaRNN	Benign	0.0035	T;T
MetaSVM	Benign	-0.86	T
MutationTaster	Benign	0.031	P;P;P;P;P
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.67	N;N
REVEL	Benign	0.27
Sift	Benign	0.18	T;T
Sift4G	Benign	0.18	T;T
Polyphen		0.49	P;D
Vest4		0.23
MPC		0.066
ClinPred		0.010	T
GERP RS		4.5
Varity_R		0.084
gMVP		0.44

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: rs62489646; hg19: chr7-150873754; COSMIC: COSV51996203; COSMIC: COSV51996203;