rs77615410

Positions:

• chr7-151186506-G-A

Variant summary

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

The ENST00000420175.3(ASB10):​c.470C>T​(p.Ala157Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0108 in 1,602,050 control chromosomes in the GnomAD database, including 1,301 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 (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (177 hom., cov: 33)
  • Exomes 𝑓: 0.0096 (1124 hom.)
• Consequence: ASB10 ENST00000420175.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3 O:1
• Conservation: PhyloP100: 1.87

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=0.004033804).
• BP6: Variant 7-151186506-G-A is Benign according to our data. Variant chr7-151186506-G-A is described in ClinVar as [Benign]. Clinvar id is 99955.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASB10	NM_001142459.2	c.470C>T	p.Ala157Val	missense_variant	2/6	ENST00000420175.3	NP_001135931.2
ASB10	NM_080871.4	c.425C>T	p.Ala142Val	missense_variant	2/6		NP_543147.2
ASB10	NM_001142460.1	c.470C>T	p.Ala157Val	missense_variant	2/5		NP_001135932.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASB10	ENST00000420175.3	c.470C>T	p.Ala157Val	missense_variant	2/6	1	NM_001142459.2	ENSP00000391137	P4
ASB10	ENST00000275838.5	c.470C>T	p.Ala157Val	missense_variant	2/5	1		ENSP00000275838
ASB10	ENST00000377867.7	c.425C>T	p.Ala142Val	missense_variant	2/6	2		ENSP00000367098	A1

Frequencies

GnomAD3 genomes AF: 0.0221 AC: 3358 AN: 152214 Hom.: 179 Cov.: 33

Gnomad AFR AF: 0.0399

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0211

Gnomad ASJ AF: 0.00951

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.0116

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000661

Gnomad OTH AF: 0.0167

GnomAD3 exomes AF: 0.0279 AC: 6243 AN: 224016 Hom.: 519 AF XY: 0.0248 AC XY: 3020 AN XY: 121884

Gnomad AFR exome AF: 0.0392

Gnomad AMR exome AF: 0.0434

Gnomad ASJ exome AF: 0.00863

Gnomad EAS exome AF: 0.239

Gnomad SAS exome AF: 0.00455

Gnomad FIN exome AF: 0.000371

Gnomad NFE exome AF: 0.000744

Gnomad OTH exome AF: 0.0153

GnomAD4 exome AF: 0.00958 AC: 13885 AN: 1449718 Hom.: 1124 Cov.: 31 AF XY: 0.00929 AC XY: 6694 AN XY: 720212

Gnomad4 AFR exome AF: 0.0382

Gnomad4 AMR exome AF: 0.0412

Gnomad4 ASJ exome AF: 0.00696

Gnomad4 EAS exome AF: 0.223

Gnomad4 SAS exome AF: 0.00551

Gnomad4 FIN exome AF: 0.000212

Gnomad4 NFE exome AF: 0.000345

Gnomad4 OTH exome AF: 0.0182

GnomAD4 genome AF: 0.0221 AC: 3363 AN: 152332 Hom.: 177 Cov.: 33 AF XY: 0.0226 AC XY: 1685 AN XY: 74492

Gnomad4 AFR AF: 0.0399

Gnomad4 AMR AF: 0.0211

Gnomad4 ASJ AF: 0.00951

Gnomad4 EAS AF: 0.233

Gnomad4 SAS AF: 0.0122

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000662

Gnomad4 OTH AF: 0.0170

Alfa AF: 0.0104 Hom.: 113

Bravo AF: 0.0256

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0398 AC: 175

ESP6500EA AF: 0.00151 AC: 13

ExAC AF: 0.0247 AC: 2986

Asia WGS AF: 0.0990 AC: 342 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3 Other:1

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	Aug 25, 2018	This variant is associated with the following publications: (PMID: 22156576, 27884173, 22798626) -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

Glaucoma 1, open angle, F Other:1

not provided, no classification provided

literature only

Casey Eye Institute Glaucoma Genetics Lab

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.015	.;.;T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.81	T;T;T
MetaRNN	Benign	0.0040	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L;.;L
MutationTaster	Benign	1.0	P;P;P;P;P
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Benign	0.048
Sift	Benign	0.26	T;T;T
Sift4G	Benign	0.33	T;T;T
Polyphen		0.0010, 0.0040	.;B;B
Vest4		0.14
MPC		0.051
ClinPred		0.0023	T
GERP RS		2.5
Varity_R		0.067
gMVP		0.23

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: rs77615410; hg19: chr7-150883593; COSMIC: COSV51995100; COSMIC: COSV51995100;