7-151186411-G-T

Variant names:

• chr7-151186411-G-T
• rs104886473
• NM_001142459.2:c.565C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001142459.2(ASB10):​c.565C>A​(p.Arg189Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000697 in 1,435,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: ASB10 NM_001142459.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.228
• 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: AD, Unknown Classification: LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP7: Synonymous conserved (PhyloP=0.228 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASB10	NM_001142459.2	c.565C>A	p.Arg189Arg	synonymous_variant	Exon 2 of 6	ENST00000420175.3	NP_001135931.2
ASB10	NM_080871.4	c.520C>A	p.Arg174Arg	synonymous_variant	Exon 2 of 6		NP_543147.2
ASB10	NM_001142460.1	c.565C>A	p.Arg189Arg	synonymous_variant	Exon 2 of 5		NP_001135932.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASB10	ENST00000420175.3	c.565C>A	p.Arg189Arg	synonymous_variant	Exon 2 of 6	1	NM_001142459.2	ENSP00000391137.2
ASB10	ENST00000275838.5	c.565C>A	p.Arg189Arg	synonymous_variant	Exon 2 of 5	1		ENSP00000275838.1
ASB10	ENST00000377867.7	c.520C>A	p.Arg174Arg	synonymous_variant	Exon 2 of 6	2		ENSP00000367098.3
ASB10	ENST00000415615.1	n.*609C>A		downstream_gene_variant		4		ENSP00000410871.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.97e-7 AC: 1 AN: 1435050 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 711338

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32930

American (AMR) AF: 0.0000245 AC: 1 AN: 40834

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25544

East Asian (EAS) AF: 0.00 AC: 0 AN: 38240

South Asian (SAS) AF: 0.00 AC: 0 AN: 82284

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51210

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5480

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1099174

Other (OTH) AF: 0.00 AC: 0 AN: 59354

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	6.0
DANN	Benign	0.76
PhyloP100		0.23

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: rs104886473; hg19: chr7-150883498;