rs104886475

Variant names:

• chr7-151181329-C-T
• rs104886475
• NM_001142459.2:c.714G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_001142459.2(ASB10):​c.714G>A​(p.Gly238Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00065 in 1,613,194 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 Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00037 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00068 (1 hom.)
• Consequence: ASB10 NM_001142459.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1 O:1
• Conservation: PhyloP100: -1.75
• Publications: 0 publications found

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]

ASB10 Gene-Disease associations (from GenCC):

• glaucoma 1, open angle, F

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 7-151181329-C-T is Benign according to our data. Variant chr7-151181329-C-T is described in ClinVar as Benign. ClinVar VariationId is 99986.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.75 with no splicing effect.
• BS2: High AC in GnomAd4 at 56 Unknown,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142459.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB10	NM_001142459.2	MANE Select	c.714G>A	p.Gly238Gly	synonymous	Exon 3 of 6	NP_001135931.2	Q8WXI3-1
	ASB10	NM_080871.4		c.669G>A	p.Gly223Gly	synonymous	Exon 3 of 6	NP_543147.2	Q8WXI3-3
	ASB10	NM_001142460.1		c.714G>A	p.Gly238Gly	synonymous	Exon 3 of 5	NP_001135932.2	Q8WXI3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB10	ENST00000420175.3	TSL:1 MANE Select	c.714G>A	p.Gly238Gly	synonymous	Exon 3 of 6	ENSP00000391137.2	Q8WXI3-1
	ASB10	ENST00000275838.5	TSL:1	c.714G>A	p.Gly238Gly	synonymous	Exon 3 of 5	ENSP00000275838.1	Q8WXI3-2
	ASB10	ENST00000968508.1		c.714G>A	p.Gly238Gly	synonymous	Exon 3 of 6	ENSP00000638567.1

Frequencies

GnomAD3 genomes AF: 0.000368 AC: 56 AN: 152192 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000750

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000405 AC: 101 AN: 249494 AF XY: 0.000354

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000463

Gnomad NFE exome AF: 0.000748

Gnomad OTH exome AF: 0.000492

GnomAD4 exome AF: 0.000679 AC: 992 AN: 1460884 Hom.: 1 Cov.: 34 AF XY: 0.000643 AC XY: 467 AN XY: 726750

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.000134 AC: 6 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.000400 AC: 21 AN: 52490

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000850 AC: 945 AN: 1111954

Other (OTH) AF: 0.000298 AC: 18 AN: 60386

GnomAD4 genome AF: 0.000368 AC: 56 AN: 152310 Hom.: 0 Cov.: 32 AF XY: 0.000416 AC XY: 31 AN XY: 74482

African (AFR) AF: 0.0000481 AC: 2 AN: 41574

American (AMR) AF: 0.000131 AC: 2 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000750 AC: 51 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000533 Hom.: 0

Bravo AF: 0.000359

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000709

EpiControl AF: 0.000771

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	-	Glaucoma 1, open angle, F (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	3.3
DANN	Benign	0.59
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs104886475; hg19: chr7-150878416; COSMIC: COSV52000069;