rs147737381

chr7-151186850-C-T

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.281G>A(p.Arg94Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000354 in 1,609,346 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00093 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00029 (0 hom.)
• Consequence: ASB10 NM_001142459.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1 O:1
• Conservation: PhyloP100: 2.17

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=0.010080278).
• BP6: Variant 7-151186850-C-T is Benign according to our data. Variant chr7-151186850-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 99976.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 139 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASB10	NM_001142459.2	c.281G>A	p.Arg94Gln	missense_variant	1/6	ENST00000420175.3
ASB10	NM_001142460.1	c.281G>A	p.Arg94Gln	missense_variant	1/5
ASB10	NM_080871.4	c.272-191G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASB10	ENST00000420175.3	c.281G>A	p.Arg94Gln	missense_variant	1/6	1	NM_001142459.2	P4
ASB10	ENST00000275838.5	c.281G>A	p.Arg94Gln	missense_variant	1/5	1
ASB10	ENST00000377867.7	c.272-191G>A		intron_variant		2		A1
ASB10	ENST00000415615.1	c.*325G>A		3_prime_UTR_variant, NMD_transcript_variant	2/3	4

Frequencies

GnomAD3 genomes AF: 0.000913 AC: 139 AN: 152196 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00297

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.000958

GnomAD3 exomes AF: 0.000272 AC: 67 AN: 246006 Hom.: 0 AF XY: 0.000225 AC XY: 30 AN XY: 133232

Gnomad AFR exome AF: 0.00285

Gnomad AMR exome AF: 0.0000584

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000173

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000294 AC: 428 AN: 1457032 Hom.: 0 Cov.: 35 AF XY: 0.000267 AC XY: 193 AN XY: 724024

Gnomad4 AFR exome AF: 0.00257

Gnomad4 AMR exome AF: 0.000112

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000288

Gnomad4 OTH exome AF: 0.000299

GnomAD4 genome AF: 0.000932 AC: 142 AN: 152314 Hom.: 0 Cov.: 32 AF XY: 0.000913 AC XY: 68 AN XY: 74468

Gnomad4 AFR AF: 0.00303

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.000948

Alfa AF: 0.000270 Hom.: 0

Bravo AF: 0.00115

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00182 AC: 8

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000305 AC: 37

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000357

ClinVar

Significance: Likely benign

Submissions summary: Benign:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 10, 2018

See Variant Classification Assertion Criteria. -

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	0.094
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.41
Cadd	Benign	20
Dann	Uncertain	1.0
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.075
FATHMM_MKL	Benign	0.37	N
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.054	D
MetaRNN	Benign	0.010	T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.53	N;N
MutationTaster	Benign	0.53	D;D;D;N;N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.10	N;N
REVEL	Benign	0.081
Sift	Benign	0.095	T;D
Sift4G	Benign	0.20	T;T
Polyphen		0.47	.;P
Vest4		0.23
MVP		0.57
MPC		0.057
ClinPred		0.031	T
GERP RS		3.8
Varity_R		0.055
gMVP		0.51

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: rs147737381; hg19: chr7-150883937; COSMIC: COSV51999149; COSMIC: COSV51999149;