7-151176244-C-T

Position:

• chr7-151176244-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_001142459.2(ASB10):​c.1272G>A​(p.Ser424Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0125 in 1,592,216 control chromosomes in the GnomAD database, including 193 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0082 (7 hom., cov: 33)
  • Exomes 𝑓: 0.013 (186 hom.)
• Consequence: ASB10 NM_001142459.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4 O:1
• Conservation: PhyloP100: -2.12

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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP6: Variant 7-151176244-C-T is Benign according to our data. Variant chr7-151176244-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 99951.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.12 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0129 (18602/1439976) while in subpopulation NFE AF= 0.0157 (17280/1101966). AF 95% confidence interval is 0.0155. There are 186 homozygotes in gnomad4_exome. There are 8903 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1248 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASB10	NM_001142459.2	c.1272G>A	p.Ser424Ser	synonymous_variant	5/6	ENST00000420175.3	NP_001135931.2
ASB10	NM_080871.4	c.1227G>A	p.Ser409Ser	synonymous_variant	5/6		NP_543147.2
ASB10	NM_001142460.1	c.1158G>A	p.Ser386Ser	synonymous_variant	4/5		NP_001135932.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASB10	ENST00000420175.3	c.1272G>A	p.Ser424Ser	synonymous_variant	5/6	1	NM_001142459.2	ENSP00000391137.2
ASB10	ENST00000275838.5	c.1158G>A	p.Ser386Ser	synonymous_variant	4/5	1		ENSP00000275838.1
ASB10	ENST00000377867.7	c.1227G>A	p.Ser409Ser	synonymous_variant	5/6	2		ENSP00000367098.3

Frequencies

GnomAD3 genomes AF: 0.00821 AC: 1249 AN: 152122 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.00246

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.00681

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0146

Gnomad OTH AF: 0.00861

GnomAD3 exomes AF: 0.00766 AC: 1752 AN: 228750 Hom.: 17 AF XY: 0.00755 AC XY: 941 AN XY: 124636

Gnomad AFR exome AF: 0.00257

Gnomad AMR exome AF: 0.00571

Gnomad ASJ exome AF: 0.00490

Gnomad EAS exome AF: 0.000113

Gnomad SAS exome AF: 0.00104

Gnomad FIN exome AF: 0.00176

Gnomad NFE exome AF: 0.0134

Gnomad OTH exome AF: 0.00905

GnomAD4 exome AF: 0.0129 AC: 18602 AN: 1439976 Hom.: 186 Cov.: 32 AF XY: 0.0125 AC XY: 8903 AN XY: 714810

Gnomad4 AFR exome AF: 0.00235

Gnomad4 AMR exome AF: 0.00547

Gnomad4 ASJ exome AF: 0.00422

Gnomad4 EAS exome AF: 0.0000507

Gnomad4 SAS exome AF: 0.00107

Gnomad4 FIN exome AF: 0.00234

Gnomad4 NFE exome AF: 0.0157

Gnomad4 OTH exome AF: 0.0117

GnomAD4 genome AF: 0.00820 AC: 1248 AN: 152240 Hom.: 7 Cov.: 33 AF XY: 0.00709 AC XY: 528 AN XY: 74426

Gnomad4 AFR AF: 0.00245

Gnomad4 AMR AF: 0.00673

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.000943

Gnomad4 NFE AF: 0.0146

Gnomad4 OTH AF: 0.00852

Alfa AF: 0.0109 Hom.: 5

Bravo AF: 0.00880

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2023	ASB10: BP4, BP7, BS1, BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 18, 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
BayesDel_noAF	Benign	-0.33
CADD	Benign	0.89
DANN	Benign	0.90

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: rs104886486; hg19: chr7-150873331;