7-151181233-G-A

Variant names:

• chr7-151181233-G-A
• rs104886478
• NM_001142459.2:c.810C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 1P and 3B. PP5 BP4 BP7 BS2_Supporting

The NM_001142459.2(ASB10):​c.810C>T​(p.Thr270Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000207 in 1,613,074 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.00032 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00020 (1 hom.)
• Consequence: ASB10 NM_001142459.2 synonymous
• Clinical Significance: not provided no classification provided P:1 O:1
• Conservation: PhyloP100: -1.84

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PP5: Variant 7-151181233-G-A is Pathogenic according to our data. Variant chr7-151181233-G-A is described in ClinVar as [not_provided]. Clinvar id is 50951.We mark this variant Likely_pathogenic, oryginal submissions are: {Pathogenic=1, not_provided=1}.
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87). . Strength limited to SUPPORTING due to the PP5.
• BP7: Synonymous conserved (PhyloP=-1.84 with no splicing effect.
• BS2: High AC in GnomAd4 at 48 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASB10	NM_001142459.2	c.810C>T	p.Thr270Thr	synonymous_variant	Exon 3 of 6	ENST00000420175.3	NP_001135931.2
ASB10	NM_080871.4	c.765C>T	p.Thr255Thr	synonymous_variant	Exon 3 of 6		NP_543147.2
ASB10	NM_001142460.1	c.810C>T	p.Thr270Thr	synonymous_variant	Exon 3 of 5		NP_001135932.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASB10	ENST00000420175.3	c.810C>T	p.Thr270Thr	synonymous_variant	Exon 3 of 6	1	NM_001142459.2	ENSP00000391137.2
ASB10	ENST00000275838.5	c.810C>T	p.Thr270Thr	synonymous_variant	Exon 3 of 5	1		ENSP00000275838.1
ASB10	ENST00000377867.7	c.765C>T	p.Thr255Thr	synonymous_variant	Exon 3 of 6	2		ENSP00000367098.3

Frequencies

GnomAD3 genomes AF: 0.000315 AC: 48 AN: 152244 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00395

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000500 AC: 124 AN: 248062 AF XY: 0.000475

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00429

Gnomad NFE exome AF: 0.000117

Gnomad OTH exome AF: 0.000494

GnomAD4 exome AF: 0.000196 AC: 286 AN: 1460712 Hom.: 1 Cov.: 34 AF XY: 0.000201 AC XY: 146 AN XY: 726696

Gnomad4 AFR exome AF: 0.0000299 AC: 1 AN: 33478

Gnomad4 AMR exome AF: 0.00 AC: 0 AN: 44710

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 26114

Gnomad4 EAS exome AF: 0.0000252 AC: 1 AN: 39696

Gnomad4 SAS exome AF: 0.000348 AC: 30 AN: 86246

Gnomad4 FIN exome AF: 0.00378 AC: 198 AN: 52412

Gnomad4 NFE exome AF: 0.0000378 AC: 42 AN: 1111914

Gnomad4 Remaining exome AF: 0.000232 AC: 14 AN: 60376

GnomAD4 genome AF: 0.000315 AC: 48 AN: 152362 Hom.: 0 Cov.: 32 AF XY: 0.000470 AC XY: 35 AN XY: 74510

Gnomad4 AFR AF: 0.00 AC: 0 AN: 0

Gnomad4 AMR AF: 0.00 AC: 0 AN: 0

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.000193 AC: 0.000192753 AN: 0.000192753

Gnomad4 SAS AF: 0.000621 AC: 0.000621375 AN: 0.000621375

Gnomad4 FIN AF: 0.00395 AC: 0.00395257 AN: 0.00395257

Gnomad4 NFE AF: 0.0000147 AC: 0.0000146972 AN: 0.0000146972

Gnomad4 OTH AF: 0.00 AC: 0 AN: 0

Alfa AF: 0.000136 Hom.: 0

Bravo AF: 0.0000340

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: not provided

Submissions summary: Pathogenic:1 Other:1

Revision: no classification provided

Submissions by phenotype

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

Mar 15, 2012

OMIM

Significance: Pathogenic

Review Status: flagged submission

Collection Method: literature only

- -

-

Casey Eye Institute Glaucoma Genetics Lab

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.15
DANN	Benign	0.62
Mutation Taster		=100/0	disease causing (ClinVar)

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: rs104886478; hg19: chr7-150878320; COSMIC: COSV51995574;