7-151187179-CAGAGAG-CAGAGAGAGAG

Variant names:

• chr7-151187179-C-CAGAG
• rs34383739
• NM_001142459.2:c.-53_-50dupCTCT

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BS2_Supporting

The NM_001142459.2(ASB10):​c.-53_-50dupCTCT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000177 in 1,495,042 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000067 (0 hom., cov: 22)
  • Exomes 𝑓: 0.00019 (0 hom.)
• Consequence: ASB10 NM_001142459.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.160
• Publications: 3 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 -1 ACMG points.

• BS2: High AC in GnomAd4 at 10 AD,Unknown 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.-53_-50dupCTCT		5_prime_UTR_variant	Exon 1 of 6	ENST00000420175.3	NP_001135931.2
ASB10	NM_001142460.1	c.-53_-50dupCTCT		5_prime_UTR_variant	Exon 1 of 5		NP_001135932.2
ASB10	NM_080871.4	c.271+269_271+272dupCTCT		intron_variant	Intron 1 of 5		NP_543147.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASB10	ENST00000420175.3	c.-53_-50dupCTCT		5_prime_UTR_variant	Exon 1 of 6	1	NM_001142459.2	ENSP00000391137.2
ASB10	ENST00000275838.5	c.-53_-50dupCTCT		5_prime_UTR_variant	Exon 1 of 5	1		ENSP00000275838.1
ASB10	ENST00000377867.7	c.271+269_271+272dupCTCT		intron_variant	Intron 1 of 5	2		ENSP00000367098.3
ASB10	ENST00000415615.1	n.*121+71_*121+74dupCTCT		intron_variant	Intron 1 of 2	4		ENSP00000410871.1

Frequencies

GnomAD3 genomes AF: 0.0000666 AC: 10 AN: 150242 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.0000976

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000741

Gnomad OTH AF: 0.000484

GnomAD2 exomes AF: 0.000309 AC: 31 AN: 100302 AF XY: 0.000319

Gnomad AFR exome AF: 0.000361

Gnomad AMR exome AF: 0.0000616

Gnomad ASJ exome AF: 0.000492

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000514

Gnomad NFE exome AF: 0.000413

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000190 AC: 255 AN: 1344800 Hom.: 0 Cov.: 0 AF XY: 0.000209 AC XY: 139 AN XY: 663796

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

African (AFR) AF: 0.000262 AC: 8 AN: 30530

American (AMR) AF: 0.0000574 AC: 2 AN: 34834

Ashkenazi Jewish (ASJ) AF: 0.000165 AC: 4 AN: 24214

East Asian (EAS) AF: 0.0000576 AC: 2 AN: 34738

South Asian (SAS) AF: 0.000143 AC: 11 AN: 77018

European-Finnish (FIN) AF: 0.000126 AC: 6 AN: 47446

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5534

European-Non Finnish (NFE) AF: 0.000210 AC: 217 AN: 1034418

Other (OTH) AF: 0.0000892 AC: 5 AN: 56068

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000666 AC: 10 AN: 150242 Hom.: 0 Cov.: 22 AF XY: 0.0000546 AC XY: 4 AN XY: 73300

African (AFR) AF: 0.0000976 AC: 4 AN: 40982

American (AMR) AF: 0.00 AC: 0 AN: 15100

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3450

East Asian (EAS) AF: 0.00 AC: 0 AN: 5106

South Asian (SAS) AF: 0.00 AC: 0 AN: 4762

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10114

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000741 AC: 5 AN: 67434

Other (OTH) AF: 0.000484 AC: 1 AN: 2068

Alfa AF: 0.0000504 Hom.: 177

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.16

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs34383739; hg19: chr7-150884266;