Genetic Variant NM_001142459.2:c.-53_-50delCTCT (chr7-151187179-CAGAG-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001142459.2(ASB10):c.-53_-50delCTCT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000152 in 1,488,790 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 22)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

ASB10
NM_001142459.2 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.639

Publications

3 publications found

Variant links:

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)

ASB10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ASB10	NM_001142459.2 link	c.-53_-50delCTCT	5_prime_UTR_variant	Exon 1 of 6	ENST00000420175.3	NP_001135931.2	Q8WXI3-1
ASB10	NM_001142460.1 link	c.-53_-50delCTCT	5_prime_UTR_variant	Exon 1 of 5		NP_001135932.2	Q8WXI3-2A0A090N8I2
ASB10	NM_080871.4 link	c.271+269_271+272delCTCT	intron_variant	Intron 1 of 5		NP_543147.2	Q8WXI3-3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ASB10	ENST00000420175.3 link	c.-53_-50delCTCT	5_prime_UTR_variant	Exon 1 of 6	1	NM_001142459.2	ENSP00000391137.2	Q8WXI3-1
ASB10	ENST00000275838.5 link	c.-53_-50delCTCT	5_prime_UTR_variant	Exon 1 of 5	1		ENSP00000275838.1	Q8WXI3-2
ASB10	ENST00000377867.7 link	c.271+269_271+272delCTCT	intron_variant	Intron 1 of 5	2		ENSP00000367098.3	Q8WXI3-3
ASB10	ENST00000415615.1 link	n.121+71_121+74delCTCT	intron_variant	Intron 1 of 2	4		ENSP00000410871.1	F8WB38

Frequencies

GnomAD3 genomes

AF:

0.0000200

AC:

AN:

150224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000196

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000297

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000947

AC:

AN:

100302

AF XY:

0.00107

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000678

Gnomad ASJ exome

AF:

0.00115

Gnomad EAS exome

AF:

0.000661

Gnomad FIN exome

AF:

0.000720

Gnomad NFE exome

AF:

0.00111

Gnomad OTH exome

AF:

0.000340

GnomAD4 exome

AF:

0.000167

AC:

223

AN:

1338470

Hom.:

AF XY:

0.000210

AC XY:

139

AN XY:

660408

show subpopulations

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

African (AFR)

AF:

0.000231

AC:

AN:

30368

American (AMR)

AF:

0.000667

AC:

AN:

34474

Ashkenazi Jewish (ASJ)

AF:

0.000290

AC:

AN:

24110

East Asian (EAS)

AF:

0.00

AC:

AN:

34530

South Asian (SAS)

AF:

0.000524

AC:

AN:

76358

European-Finnish (FIN)

AF:

0.000255

AC:

AN:

47140

Middle Eastern (MID)

AF:

0.000181

AC:

AN:

5522

European-Non Finnish (NFE)

AF:

0.000124

AC:

128

AN:

1030182

Other (OTH)

AF:

0.0000896

AC:

AN:

55786

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.264

Heterozygous variant carriers

100

134

167

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000200

AC:

AN:

150320

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73394

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41092

American (AMR)

AF:

0.00

AC:

AN:

15114

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3450

East Asian (EAS)

AF:

0.000196

AC:

AN:

5092

South Asian (SAS)

AF:

0.00

AC:

AN:

4756

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10106

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000297

AC:

AN:

67422

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00307

Hom.:

177

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.64

Mutation Taster

=121/79

disease causing (fs/PTC)

(source)

Splicing

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

Publications

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NM_001142459.2:c.-53_-50delCTCT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over