Genetic Variant ASB10:c.-53_-50dupCTCT (chr7-151187179-C-CAGAG) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BS2_Supporting

The NM_001142459.2(ASB10):c.-53_-50dupCTCT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000177 in 1,495,042 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 0.000067 ( 0 hom., cov: 22)

Exomes 𝑓: 0.00019 ( 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BS2

High AC in GnomAd4 at 10 AD,Unknown gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

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.-53_-50dupCTCT	5_prime_UTR	Exon 1 of 6	NP_001135931.2
ASB10	NM_001142460.1		c.-53_-50dupCTCT	5_prime_UTR	Exon 1 of 5	NP_001135932.2
ASB10	NM_080871.4		c.271+269_271+272dupCTCT	intron	N/A	NP_543147.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ASB10	ENST00000420175.3	TSL:1 MANE Select	c.-53_-50dupCTCT	5_prime_UTR	Exon 1 of 6	ENSP00000391137.2
ASB10	ENST00000275838.5	TSL:1	c.-53_-50dupCTCT	5_prime_UTR	Exon 1 of 5	ENSP00000275838.1
ASB10	ENST00000377867.7	TSL:2	c.271+269_271+272dupCTCT	intron	N/A	ENSP00000367098.3

Frequencies

GnomAD3 genomes

AF:

0.0000666

AC:

AN:

150242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000976

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:

0.0000741

Gnomad OTH

AF:

0.000484

GnomAD2 exomes

AF:

0.000309

AC:

AN:

100302

AF XY:

0.000319

show subpopulations

Gnomad AFR exome

AF:

0.000361

Gnomad AMR exome

AF:

0.0000616

Gnomad ASJ exome

AF:

0.000492

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000514

Gnomad NFE exome

AF:

0.000413

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000190

AC:

255

AN:

1344800

Hom.:

Cov.:

AF XY:

0.000209

AC XY:

139

AN XY:

663796

show subpopulations

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

African (AFR)

AF:

0.000262

AC:

AN:

30530

American (AMR)

AF:

0.0000574

AC:

AN:

34834

Ashkenazi Jewish (ASJ)

AF:

0.000165

AC:

AN:

24214

East Asian (EAS)

AF:

0.0000576

AC:

AN:

34738

South Asian (SAS)

AF:

0.000143

AC:

AN:

77018

European-Finnish (FIN)

AF:

0.000126

AC:

AN:

47446

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5534

European-Non Finnish (NFE)

AF:

0.000210

AC:

217

AN:

1034418

Other (OTH)

AF:

0.0000892

AC:

AN:

56068

⚠️ 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: 0.314

Heterozygous variant carriers

101

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:

0.0000666

AC:

AN:

150242

Hom.:

Cov.:

AF XY:

0.0000546

AC XY:

AN XY:

73300

show subpopulations

African (AFR)

AF:

0.0000976

AC:

AN:

40982

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:

0.0000741

AC:

AN:

67434

Other (OTH)

AF:

0.000484

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

Age Distribution

Genome 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

Alfa

AF:

0.0000504

Hom.:

177

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.16

Splicing

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

Publications

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7-151187179-CAGAGAG-CAGAGAGAGAG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over