Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001142459.2(ASB10):c.224C>A(p.Ala75Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00117 in 1,614,034 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A75V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0058 ( 9 hom., cov: 32)

Exomes 𝑓: 0.00068 ( 11 hom. )

Consequence

ASB10
NM_001142459.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3O:1

Conservation

PhyloP100: 1.60

Publications

1 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: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0035480857).

BP6

Variant 7-151186907-G-T is Benign according to our data. Variant chr7-151186907-G-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 99944.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00585 (891/152346) while in subpopulation AFR AF = 0.0196 (817/41580). AF 95% confidence interval is 0.0185. There are 9 homozygotes in GnomAd4. There are 393 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 891 AD,Unknown gene.

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	HGVSp	Effect	Exon Rank	Protein
ASB10	NM_001142459.2	MANE Select	c.224C>A	p.Ala75Glu	missense	Exon 1 of 6	NP_001135931.2
ASB10	NM_001142460.1		c.224C>A	p.Ala75Glu	missense	Exon 1 of 5	NP_001135932.2
ASB10	NM_080871.4		c.272-248C>A		intron	N/A	NP_543147.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ASB10	ENST00000420175.3	TSL:1 MANE Select	c.224C>A	p.Ala75Glu	missense	Exon 1 of 6	ENSP00000391137.2
ASB10	ENST00000275838.5	TSL:1	c.224C>A	p.Ala75Glu	missense	Exon 1 of 5	ENSP00000275838.1
ASB10	ENST00000415615.1	TSL:4	n.*268C>A		non_coding_transcript_exon	Exon 2 of 3	ENSP00000410871.1

Frequencies

GnomAD3 genomes

AF:

0.00586

AC:

892

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0197

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00382

GnomAD2 exomes

AF:

0.00164

AC:

408

AN:

249188

AF XY:

0.00118

show subpopulations

Gnomad AFR exome

AF:

0.0218

Gnomad AMR exome

AF:

0.00110

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000895

Gnomad OTH exome

AF:

0.000654

GnomAD4 exome

AF:

0.000683

AC:

999

AN:

1461688

Hom.:

Cov.:

AF XY:

0.000593

AC XY:

431

AN XY:

727168

show subpopulations

African (AFR)

AF:

0.0236

AC:

790

AN:

33480

American (AMR)

AF:

0.00130

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000464

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53244

Middle Eastern (MID)

AF:

0.00156

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000369

AC:

AN:

1111996

Other (OTH)

AF:

0.00161

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

116

175

233

291

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<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:

0.00585

AC:

891

AN:

152346

Hom.:

Cov.:

AF XY:

0.00528

AC XY:

393

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.0196

AC:

817

AN:

41580

American (AMR)

AF:

0.00392

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68036

Other (OTH)

AF:

0.00378

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

139

186

232

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00114

Hom.:

Bravo

AF:

0.00723

ESP6500AA

AF:

0.0166

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00189

AC:

230

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000296

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Glaucoma 1, open angle, F (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.66

DEOGEN2

Benign

0.010

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.091

LIST_S2

Benign

0.68

MetaRNN

Benign

0.0035

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.33

PhyloP100

1.6

PrimateAI

Benign

0.41

PROVEAN

Benign

0.40

REVEL

Benign

0.10

Sift

Benign

0.94

Sift4G

Benign

1.0

Polyphen

0.38

Vest4

0.28

MVP

0.23

MPC

0.10

ClinPred

0.016

GERP RS

4.4

PromoterAI

-0.0020

Neutral

(source)

Varity_R

0.12

gMVP

0.17

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over