rs61735130

chr7-151181133-G-Achr7-151181133-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001142459.2(ASB10):c.910C>T(p.Arg304Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00287 in 1,611,646 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R304H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0026 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0029 (12 hom.)
• Consequence: ASB10 NM_001142459.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1 O:1
• Conservation: PhyloP100: 1.52

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008752853).
• BP6: Variant 7-151181133-G-A is Benign according to our data. Variant chr7-151181133-G-A is described in ClinVar as [Benign]. Clinvar id is 99966.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 401 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASB10	NM_001142459.2	c.910C>T	p.Arg304Cys	missense_variant	3/6	ENST00000420175.3
ASB10	NM_080871.4	c.865C>T	p.Arg289Cys	missense_variant	3/6
ASB10	NM_001142460.1	c.910C>T	p.Arg304Cys	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASB10	ENST00000420175.3	c.910C>T	p.Arg304Cys	missense_variant	3/6	1	NM_001142459.2	P4
ASB10	ENST00000275838.5	c.910C>T	p.Arg304Cys	missense_variant	3/5	1
ASB10	ENST00000377867.7	c.865C>T	p.Arg289Cys	missense_variant	3/6	2		A1

Frequencies

GnomAD3 genomes AF: 0.00263 AC: 401 AN: 152232 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000772

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00190

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00772

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00320

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00299 AC: 733 AN: 245448 Hom.: 2 AF XY: 0.00305 AC XY: 408 AN XY: 133844

Gnomad AFR exome AF: 0.000702

Gnomad AMR exome AF: 0.00180

Gnomad ASJ exome AF: 0.0107

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.000393

Gnomad FIN exome AF: 0.00793

Gnomad NFE exome AF: 0.00325

Gnomad OTH exome AF: 0.00265

GnomAD4 exome AF: 0.00290 AC: 4230 AN: 1459296 Hom.: 12 Cov.: 31 AF XY: 0.00288 AC XY: 2087 AN XY: 725776

Gnomad4 AFR exome AF: 0.000508

Gnomad4 AMR exome AF: 0.00175

Gnomad4 ASJ exome AF: 0.00962

Gnomad4 EAS exome AF: 0.0000757

Gnomad4 SAS exome AF: 0.000394

Gnomad4 FIN exome AF: 0.00816

Gnomad4 NFE exome AF: 0.00290

Gnomad4 OTH exome AF: 0.00302

GnomAD4 genome AF: 0.00263 AC: 401 AN: 152350 Hom.: 2 Cov.: 33 AF XY: 0.00282 AC XY: 210 AN XY: 74494

Gnomad4 AFR AF: 0.000769

Gnomad4 AMR AF: 0.00189

Gnomad4 ASJ AF: 0.00922

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00772

Gnomad4 NFE AF: 0.00320

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00322 Hom.: 0

Bravo AF: 0.00227

TwinsUK AF: 0.00189 AC: 7

ALSPAC AF: 0.00259 AC: 10

ESP6500AA AF: 0.000455 AC: 2

ESP6500EA AF: 0.00373 AC: 32

ExAC AF: 0.00271 AC: 329

EpiCase AF: 0.00360

EpiControl AF: 0.00445

ClinVar

Significance: Benign

Submissions summary: Benign:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 17, 2024

- -

Glaucoma 1, open angle, F Other:1

not provided, no classification provided

literature only

Casey Eye Institute Glaucoma Genetics Lab

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.35
Cadd	Pathogenic	29
Dann	Pathogenic	1.0
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Benign	0.074	D
MetaRNN	Benign	0.0088	T;T;T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	0.76	N;.;N
MutationTaster	Benign	0.98	D;D;D;D;D
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.9	N;D;N
REVEL	Benign	0.23
Sift	Uncertain	0.014	D;D;D
Sift4G	Uncertain	0.027	D;D;D
Polyphen		1.0, 1.0	.;D;D
Vest4		0.47
MVP		0.63
MPC		0.31
ClinPred		0.023	T
GERP RS		5.3
Varity_R		0.10
gMVP		0.31

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: rs61735130; hg19: chr7-150878220; COSMIC: COSV52000032;