7-151176577-G-T

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.1204C>A(p.Pro402Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0336 in 1,550,964 control chromosomes in the GnomAD database, including 1,855 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 0.068 (714 hom., cov: 33)
  • Exomes 𝑓: 0.030 (1141 hom.)
• Consequence: ASB10 NM_001142459.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.66

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=0.0014445186).
• BP6: Variant 7-151176577-G-T is Benign according to our data. Variant chr7-151176577-G-T is described in ClinVar as [Benign]. Clinvar id is 1234767.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASB10	NM_001142459.2	c.1204C>A	p.Pro402Thr	missense_variant	4/6	ENST00000420175.3
ASB10	NM_080871.4	c.1159C>A	p.Pro387Thr	missense_variant	4/6
ASB10	NM_001142460.1	c.1105-280C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASB10	ENST00000420175.3	c.1204C>A	p.Pro402Thr	missense_variant	4/6	1	NM_001142459.2	P4
ASB10	ENST00000275838.5	c.1105-280C>A		intron_variant		1
ASB10	ENST00000377867.7	c.1159C>A	p.Pro387Thr	missense_variant	4/6	2		A1

Frequencies

GnomAD3 genomes AF: 0.0675 AC: 10258 AN: 152062 Hom.: 713 Cov.: 33

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.0392

Gnomad ASJ AF: 0.0579

Gnomad EAS AF: 0.0102

Gnomad SAS AF: 0.0547

Gnomad FIN AF: 0.0204

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0221

Gnomad OTH AF: 0.0607

GnomAD3 exomes AF: 0.0370 AC: 5787 AN: 156420 Hom.: 223 AF XY: 0.0373 AC XY: 3091 AN XY: 82938

Gnomad AFR exome AF: 0.178

Gnomad AMR exome AF: 0.0232

Gnomad ASJ exome AF: 0.0599

Gnomad EAS exome AF: 0.00679

Gnomad SAS exome AF: 0.0567

Gnomad FIN exome AF: 0.0173

Gnomad NFE exome AF: 0.0241

Gnomad OTH exome AF: 0.0419

GnomAD4 exome AF: 0.0299 AC: 41848 AN: 1398784 Hom.: 1141 Cov.: 32 AF XY: 0.0304 AC XY: 20969 AN XY: 689880

Gnomad4 AFR exome AF: 0.175

Gnomad4 AMR exome AF: 0.0255

Gnomad4 ASJ exome AF: 0.0613

Gnomad4 EAS exome AF: 0.0188

Gnomad4 SAS exome AF: 0.0565

Gnomad4 FIN exome AF: 0.0194

Gnomad4 NFE exome AF: 0.0233

Gnomad4 OTH exome AF: 0.0383

GnomAD4 genome AF: 0.0675 AC: 10276 AN: 152180 Hom.: 714 Cov.: 33 AF XY: 0.0671 AC XY: 4992 AN XY: 74386

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.0390

Gnomad4 ASJ AF: 0.0579

Gnomad4 EAS AF: 0.0104

Gnomad4 SAS AF: 0.0547

Gnomad4 FIN AF: 0.0204

Gnomad4 NFE AF: 0.0220

Gnomad4 OTH AF: 0.0624

Alfa AF: 0.0316 Hom.: 250

Bravo AF: 0.0735

TwinsUK AF: 0.0210 AC: 78

ALSPAC AF: 0.0259 AC: 100

ExAC AF: 0.0459 AC: 1228

Asia WGS AF: 0.0460 AC: 161 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 22, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.30
Cadd	Benign	16
Dann	Uncertain	0.99
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.74	T;T
MetaRNN	Benign	0.0014	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	P;P;P;P;P
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-2.2	N;N
REVEL	Benign	0.15
Sift	Benign	0.055	T;T
Sift4G	Uncertain	0.057	T;T
Polyphen		0.51	P;P
Vest4		0.10
MPC		0.062
ClinPred		0.019	T
GERP RS		3.7
Varity_R		0.080
gMVP		0.47

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: rs919533; hg19: chr7-150873664; COSMIC: COSV99034572; COSMIC: COSV99034572;