NM_001142459.2:c.-55_-50dupCTCTCT

Variant names:

• chr7-151187179-C-CAGAGAG
• rs34383739
• NM_001142459.2:c.-55_-50dupCTCTCT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001142459.2(ASB10):​c.-55_-50dupCTCTCT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000002 in 1,497,080 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 0.0000067 (0 hom., cov: 22)
  • Exomes 𝑓: 0.0000015 (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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASB10	NM_001142459.2	c.-55_-50dupCTCTCT		5_prime_UTR_variant	Exon 1 of 6	ENST00000420175.3	NP_001135931.2
ASB10	NM_001142460.1	c.-55_-50dupCTCTCT		5_prime_UTR_variant	Exon 1 of 5		NP_001135932.2
ASB10	NM_080871.4	c.271+267_271+272dupCTCTCT		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.-55_-50dupCTCTCT		5_prime_UTR_variant	Exon 1 of 6	1	NM_001142459.2	ENSP00000391137.2
ASB10	ENST00000275838.5	c.-55_-50dupCTCTCT		5_prime_UTR_variant	Exon 1 of 5	1		ENSP00000275838.1
ASB10	ENST00000377867.7	c.271+267_271+272dupCTCTCT		intron_variant	Intron 1 of 5	2		ENSP00000367098.3
ASB10	ENST00000415615.1	n.*121+69_*121+74dupCTCTCT		intron_variant	Intron 1 of 2	4		ENSP00000410871.1

Frequencies

GnomAD3 genomes AF: 0.00000666 AC: 1 AN: 150248 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.0000244

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000148 AC: 2 AN: 1346832 Hom.: 0 Cov.: 0 AF XY: 0.00000301 AC XY: 2 AN XY: 664744

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

African (AFR) AF: 0.0000327 AC: 1 AN: 30562

American (AMR) AF: 0.00 AC: 0 AN: 34844

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24256

East Asian (EAS) AF: 0.00 AC: 0 AN: 34738

South Asian (SAS) AF: 0.00 AC: 0 AN: 77062

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47472

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5536

European-Non Finnish (NFE) AF: 9.65e-7 AC: 1 AN: 1036240

Other (OTH) AF: 0.00 AC: 0 AN: 56122

⚠️ 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: 0.00000666 AC: 1 AN: 150248 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 73304

African (AFR) AF: 0.0000244 AC: 1 AN: 40986

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: 0.00 AC: 0 AN: 67436

Other (OTH) AF: 0.00 AC: 0 AN: 2068

Alfa AF: 0.00 Hom.: 177

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.16
Mutation Taster		=82/18	polymorphism

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;