chr7-151187179-CAG-C

Variant names:

• chr7-151187179-CAG-C
• rs34383739
• NM_001142459.2:c.-51_-50delCT

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_001142459.2(ASB10):​c.-51_-50delCT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0636 in 1,116,648 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00067 (0 hom., cov: 22)
  • Exomes 𝑓: 0.073 (0 hom.)
• Consequence: ASB10 NM_001142459.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.639
• 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 -2 ACMG points.

• BP6: Variant 7-151187179-CAG-C is Benign according to our data. Variant chr7-151187179-CAG-C is described in ClinVar as [Benign]. Clinvar id is 402399.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASB10	NM_001142459.2	c.-51_-50delCT		5_prime_UTR_variant	Exon 1 of 6	ENST00000420175.3	NP_001135931.2
ASB10	NM_001142460.1	c.-51_-50delCT		5_prime_UTR_variant	Exon 1 of 5		NP_001135932.2
ASB10	NM_080871.4	c.271+271_271+272delCT		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.-51_-50delCT		5_prime_UTR_variant	Exon 1 of 6	1	NM_001142459.2	ENSP00000391137.2
ASB10	ENST00000275838.5	c.-51_-50delCT		5_prime_UTR_variant	Exon 1 of 5	1		ENSP00000275838.1
ASB10	ENST00000377867.7	c.271+271_271+272delCT		intron_variant	Intron 1 of 5	2		ENSP00000367098.3
ASB10	ENST00000415615.1	n.*121+73_*121+74delCT		intron_variant	Intron 1 of 2	4		ENSP00000410871.1

Frequencies

GnomAD3 genomes AF: 0.000670 AC: 100 AN: 149144 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.000342

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000467

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000196

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00321

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000671

Gnomad OTH AF: 0.000974

GnomAD2 exomes AF: 0.176 AC: 17620 AN: 100302 AF XY: 0.181

Gnomad AFR exome AF: 0.135

Gnomad AMR exome AF: 0.195

Gnomad ASJ exome AF: 0.134

Gnomad EAS exome AF: 0.306

Gnomad FIN exome AF: 0.115

Gnomad NFE exome AF: 0.155

Gnomad OTH exome AF: 0.165

GnomAD4 exome AF: 0.0733 AC: 70914 AN: 967418 Hom.: 0 AF XY: 0.0784 AC XY: 37316 AN XY: 476098

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

African (AFR) AF: 0.0830 AC: 1781 AN: 21460

American (AMR) AF: 0.153 AC: 3884 AN: 25464

Ashkenazi Jewish (ASJ) AF: 0.0732 AC: 1392 AN: 19028

East Asian (EAS) AF: 0.164 AC: 2739 AN: 16734

South Asian (SAS) AF: 0.162 AC: 8705 AN: 53864

European-Finnish (FIN) AF: 0.0827 AC: 2744 AN: 33176

Middle Eastern (MID) AF: 0.0579 AC: 238 AN: 4114

European-Non Finnish (NFE) AF: 0.0614 AC: 46365 AN: 754532

Other (OTH) AF: 0.0785 AC: 3066 AN: 39046

⚠️ 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: 0.000670 AC: 100 AN: 149230 Hom.: 0 Cov.: 22 AF XY: 0.000701 AC XY: 51 AN XY: 72798

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

African (AFR) AF: 0.000341 AC: 14 AN: 41006

American (AMR) AF: 0.000466 AC: 7 AN: 15006

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3430

East Asian (EAS) AF: 0.000197 AC: 1 AN: 5078

South Asian (SAS) AF: 0.00 AC: 0 AN: 4750

European-Finnish (FIN) AF: 0.00321 AC: 31 AN: 9658

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000671 AC: 45 AN: 67028

Other (OTH) AF: 0.000965 AC: 2 AN: 2072

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0922 Hom.: 177

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: ExAC frequency -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.64
Mutation Taster		=115/85	disease causing (fs/PTC)

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; COSMIC: COSV51994810; COSMIC: COSV51994810;