rs2253592

Variant names:

• chr7-151181173-C-G
• rs2253592
• NM_001142459.2:c.870G>C
• ASB10 p.Ala290Ala

Your query was ambiguous. Multiple possible variants found:

• chr7-151181173-C-G
• chr7-151181173-C-A
• chr7-151181173-C-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001142459.2(ASB10):​c.870G>C​(p.Ala290Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 1,610,130 control chromosomes in the GnomAD database, including 127,099 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.47 (19071 hom., cov: 33)
  • Exomes 𝑓: 0.38 (108028 hom.)
• Consequence: ASB10 NM_001142459.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.65
• Publications: 19 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: AD, Unknown Classification: LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 7-151181173-C-G is Benign according to our data. Variant chr7-151181173-C-G is described in ClinVar as Benign. ClinVar VariationId is 667623.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.65 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.716 is higher than 0.05.

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.870G>C	p.Ala290Ala	synonymous	Exon 3 of 6	NP_001135931.2	Q8WXI3-1
	ASB10	NM_080871.4		c.825G>C	p.Ala275Ala	synonymous	Exon 3 of 6	NP_543147.2	Q8WXI3-3
	ASB10	NM_001142460.1		c.870G>C	p.Ala290Ala	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.870G>C	p.Ala290Ala	synonymous	Exon 3 of 6	ENSP00000391137.2	Q8WXI3-1
	ASB10	ENST00000275838.5	TSL:1	c.870G>C	p.Ala290Ala	synonymous	Exon 3 of 5	ENSP00000275838.1	Q8WXI3-2
	ASB10	ENST00000968508.1		c.870G>C	p.Ala290Ala	synonymous	Exon 3 of 6	ENSP00000638567.1

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72180 AN: 152096 Hom.: 19038 Cov.: 33

Gnomad AFR AF: 0.722

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.536

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.363

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.472

GnomAD2 exomes AF: 0.399 AC: 97166 AN: 243776 AF XY: 0.389

Gnomad AFR exome AF: 0.731

Gnomad AMR exome AF: 0.338

Gnomad ASJ exome AF: 0.464

Gnomad EAS exome AF: 0.531

Gnomad FIN exome AF: 0.389

Gnomad NFE exome AF: 0.374

Gnomad OTH exome AF: 0.389

GnomAD4 exome AF: 0.378 AC: 551455 AN: 1457916 Hom.: 108028 Cov.: 64 AF XY: 0.375 AC XY: 271961 AN XY: 724924

African (AFR) AF: 0.730 AC: 24438 AN: 33454

American (AMR) AF: 0.347 AC: 15460 AN: 44520

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 12179 AN: 26090

East Asian (EAS) AF: 0.540 AC: 21373 AN: 39586

South Asian (SAS) AF: 0.294 AC: 25335 AN: 86168

European-Finnish (FIN) AF: 0.387 AC: 20122 AN: 51936

Middle Eastern (MID) AF: 0.377 AC: 2161 AN: 5736

European-Non Finnish (NFE) AF: 0.366 AC: 406065 AN: 1110176

Other (OTH) AF: 0.404 AC: 24322 AN: 60250

GnomAD4 genome AF: 0.475 AC: 72262 AN: 152214 Hom.: 19071 Cov.: 33 AF XY: 0.468 AC XY: 34855 AN XY: 74404

African (AFR) AF: 0.722 AC: 30007 AN: 41540

American (AMR) AF: 0.386 AC: 5905 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 1611 AN: 3470

East Asian (EAS) AF: 0.536 AC: 2771 AN: 5168

South Asian (SAS) AF: 0.303 AC: 1461 AN: 4822

European-Finnish (FIN) AF: 0.379 AC: 4016 AN: 10602

Middle Eastern (MID) AF: 0.349 AC: 102 AN: 292

European-Non Finnish (NFE) AF: 0.369 AC: 25121 AN: 68000

Other (OTH) AF: 0.471 AC: 995 AN: 2114

Alfa AF: 0.359 Hom.: 3026

Bravo AF: 0.491

Asia WGS AF: 0.420 AC: 1462 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.0040
DANN	Benign	0.43
PhyloP100		-3.7
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2253592;

hg19: chr7-150878260;

COSMIC: COSV51994980;