rs104886474

chr7-151181424-C-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001142459.2(ASB10):c.619G>C(p.Val207Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00195 in 1,606,730 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (7 hom.)
• Consequence: ASB10 NM_001142459.2 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts P:1 B:3 O:1
• Conservation: PhyloP100: 2.99

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.025848866).
• BP6: Variant 7-151181424-C-G is Benign according to our data. Variant chr7-151181424-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 50953.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd at 239 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASB10	NM_001142459.2	c.619G>C	p.Val207Leu	missense_variant	3/6	ENST00000420175.3
ASB10	NM_080871.4	c.574G>C	p.Val192Leu	missense_variant	3/6
ASB10	NM_001142460.1	c.619G>C	p.Val207Leu	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASB10	ENST00000420175.3	c.619G>C	p.Val207Leu	missense_variant	3/6	1	NM_001142459.2	P4
ASB10	ENST00000275838.5	c.619G>C	p.Val207Leu	missense_variant	3/5	1
ASB10	ENST00000377867.7	c.574G>C	p.Val192Leu	missense_variant	3/6	2		A1

Frequencies

GnomAD3 genomes AF: 0.00157 AC: 239 AN: 152154 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00307

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00131 AC: 318 AN: 243510 Hom.: 1 AF XY: 0.00133 AC XY: 177 AN XY: 132730

Gnomad AFR exome AF: 0.000321

Gnomad AMR exome AF: 0.000670

Gnomad ASJ exome AF: 0.000104

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000401

Gnomad FIN exome AF: 0.0000467

Gnomad NFE exome AF: 0.00244

Gnomad OTH exome AF: 0.00200

GnomAD4 exome AF: 0.00200 AC: 2902 AN: 1454458 Hom.: 7 Cov.: 34 AF XY: 0.00195 AC XY: 1410 AN XY: 722430

Gnomad4 AFR exome AF: 0.000269

Gnomad4 AMR exome AF: 0.000674

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000280

Gnomad4 FIN exome AF: 0.000153

Gnomad4 NFE exome AF: 0.00243

Gnomad4 OTH exome AF: 0.00225

GnomAD4 genome AF: 0.00157 AC: 239 AN: 152272 Hom.: 0 Cov.: 32 AF XY: 0.00144 AC XY: 107 AN XY: 74444

Gnomad4 AFR AF: 0.000385

Gnomad4 AMR AF: 0.000458

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00307

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00183 Hom.: 0

Bravo AF: 0.00157

TwinsUK AF: 0.00216 AC: 8

ALSPAC AF: 0.00234 AC: 9

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00245 AC: 21

ExAC AF: 0.00133 AC: 161

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Pathogenic:1 Benign:3 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Glaucoma 1, open angle, F Pathogenic:1 Other:1

not provided, no classification provided	literature only	Casey Eye Institute Glaucoma Genetics Lab	-	- -
Pathogenic, no assertion criteria provided	literature only	OMIM	Mar 15, 2012	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2023	ASB10: BS1, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Sep 10, 2023	- -

ASB10-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 10, 2024

This variant is classified as likely 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	Uncertain	0.38
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.23
Cadd	Uncertain	24
Dann	Uncertain	1.0
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.87	D;D;D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.026	T;T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	0.78	N;.;N
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-2.3	N;D;N
REVEL	Benign	0.13
Sift	Uncertain	0.0060	D;D;D
Sift4G	Uncertain	0.019	D;D;D
Polyphen		0.60, 0.90	.;P;P
Vest4		0.66
MVP		0.44
MPC		0.14
ClinPred		0.023	T
GERP RS		5.1
Varity_R		0.23
gMVP		0.43

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: rs104886474; hg19: chr7-150878511;