7-151187179-CAGAGAG-CAGAGAGAG

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001142459.2(ASB10):​c.-51_-50dupCT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 1,483,822 control chromosomes in the GnomAD database, including 7,124 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (4939 hom., cov: 22)
  • Exomes 𝑓: 0.24 (2185 hom.)
• Consequence: ASB10 NM_001142459.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -16 ACMG points.

• BP6: Variant 7-151187179-C-CAG is Benign according to our data. Variant chr7-151187179-C-CAG is described in ClinVar as [Benign]. Clinvar id is 402398.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.257 AC: 38552 AN: 150140 Hom.: 4933 Cov.: 22

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.0807

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.279

GnomAD2 exomes AF: 0.280 AC: 28084 AN: 100302 AF XY: 0.278

Gnomad AFR exome AF: 0.307

Gnomad AMR exome AF: 0.265

Gnomad ASJ exome AF: 0.341

Gnomad EAS exome AF: 0.146

Gnomad FIN exome AF: 0.286

Gnomad NFE exome AF: 0.307

Gnomad OTH exome AF: 0.302

GnomAD4 exome AF: 0.238 AC: 317270 AN: 1333586 Hom.: 2185 Cov.: 0 AF XY: 0.236 AC XY: 155203 AN XY: 658378

African (AFR) AF: 0.220 AC: 6648 AN: 30218

American (AMR) AF: 0.192 AC: 6654 AN: 34608

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 7082 AN: 24076

East Asian (EAS) AF: 0.112 AC: 3878 AN: 34578

South Asian (SAS) AF: 0.184 AC: 14104 AN: 76516

European-Finnish (FIN) AF: 0.207 AC: 9770 AN: 47244

Middle Eastern (MID) AF: 0.235 AC: 1296 AN: 5512

European-Non Finnish (NFE) AF: 0.249 AC: 254906 AN: 1025192

Other (OTH) AF: 0.232 AC: 12932 AN: 55642

GnomAD4 genome AF: 0.257 AC: 38583 AN: 150236 Hom.: 4939 Cov.: 22 AF XY: 0.251 AC XY: 18388 AN XY: 73366

African (AFR) AF: 0.247 AC: 10154 AN: 41062

American (AMR) AF: 0.247 AC: 3728 AN: 15108

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 1239 AN: 3450

East Asian (EAS) AF: 0.0813 AC: 414 AN: 5092

South Asian (SAS) AF: 0.208 AC: 986 AN: 4748

European-Finnish (FIN) AF: 0.225 AC: 2271 AN: 10088

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.280 AC: 18882 AN: 67400

Other (OTH) AF: 0.280 AC: 583 AN: 2084

Alfa AF: 0.174 Hom.: 177

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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: Frequency -

not provided Benign:1

Aug 15, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.16
Mutation Taster		=176/24	polymorphism (auto)

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: COSV51995409; COSMIC: COSV51995409;