Genetic Variant ASB10:c.-55_-50dupCTCTCT (chr7-151187179-C-CAGAGAG) – ACMG Classification: Uncertain_significance (2 pts)

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

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.160

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142459.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ASB10	NM_001142459.2	MANE Select	c.-55_-50dupCTCTCT	5_prime_UTR	Exon 1 of 6	NP_001135931.2
ASB10	NM_001142460.1		c.-55_-50dupCTCTCT	5_prime_UTR	Exon 1 of 5	NP_001135932.2
ASB10	NM_080871.4		c.271+267_271+272dupCTCTCT	intron	N/A	NP_543147.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ASB10	ENST00000420175.3	TSL:1 MANE Select	c.-55_-50dupCTCTCT	5_prime_UTR	Exon 1 of 6	ENSP00000391137.2
ASB10	ENST00000275838.5	TSL:1	c.-55_-50dupCTCTCT	5_prime_UTR	Exon 1 of 5	ENSP00000275838.1
ASB10	ENST00000377867.7	TSL:2	c.271+267_271+272dupCTCTCT	intron	N/A	ENSP00000367098.3

Frequencies

GnomAD3 genomes

AF:

0.00000666

AC:

AN:

150248

Hom.:

Cov.:

show subpopulations

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:

AN:

1346832

Hom.:

Cov.:

AF XY:

0.00000301

AC XY:

AN XY:

664744

show subpopulations

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

African (AFR)

AF:

0.0000327

AC:

AN:

30562

American (AMR)

AF:

0.00

AC:

AN:

34844

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24256

East Asian (EAS)

AF:

0.00

AC:

AN:

34738

South Asian (SAS)

AF:

0.00

AC:

AN:

77062

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47472

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5536

European-Non Finnish (NFE)

AF:

9.65e-7

AC:

AN:

1036240

Other (OTH)

AF:

0.00

AC:

AN:

56122

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.250

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000666

AC:

AN:

150248

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73304

show subpopulations

African (AFR)

AF:

0.0000244

AC:

AN:

40986

American (AMR)

AF:

0.00

AC:

AN:

15100

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3450

East Asian (EAS)

AF:

0.00

AC:

AN:

5106

South Asian (SAS)

AF:

0.00

AC:

AN:

4762

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10114

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67436

Other (OTH)

AF:

0.00

AC:

AN:

2068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

177

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.16

Mutation Taster

=82/18

polymorphism

(source)

Splicing

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

Publications

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7-151187179-CAGAGAG-CAGAGAGAGAGAG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over