Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_080871.4(ASB10):c.56C>G(p.Pro19Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00386 in 1,513,956 control chromosomes in the GnomAD database, including 180 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P19S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.019 ( 100 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 80 hom. )

Consequence

ASB10
NM_080871.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2O:1

Conservation

PhyloP100: -0.0470

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=0.0022161305).

BP6

Variant 7-151187667-G-C is Benign according to our data. Variant chr7-151187667-G-C is described in ClinVar as Benign. ClinVar VariationId is 99961.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0641 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080871.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB10	NM_080871.4		c.56C>G	p.Pro19Arg	missense	Exon 1 of 6	NP_543147.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB10	ENST00000377867.7	TSL:2	c.56C>G	p.Pro19Arg	missense	Exon 1 of 6	ENSP00000367098.3
	ASB10	ENST00000415615.1	TSL:4	n.56C>G		non_coding_transcript_exon	Exon 1 of 3	ENSP00000410871.1

Frequencies

GnomAD3 genomes

AF:

0.0194

AC:

2958

AN:

152156

Hom.:

100

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0664

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00850

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000515

Gnomad OTH

AF:

0.0163

GnomAD2 exomes

AF:

0.00534

AC:

681

AN:

127568

AF XY:

0.00421

show subpopulations

Gnomad AFR exome

AF:

0.0698

Gnomad AMR exome

AF:

0.00493

Gnomad ASJ exome

AF:

0.000181

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000396

Gnomad OTH exome

AF:

0.00305

GnomAD4 exome

AF:

0.00212

AC:

2893

AN:

1361682

Hom.:

Cov.:

AF XY:

0.00186

AC XY:

1236

AN XY:

665822

show subpopulations

African (AFR)

AF:

0.0682

AC:

2112

AN:

30986

American (AMR)

AF:

0.00552

AC:

184

AN:

33328

Ashkenazi Jewish (ASJ)

AF:

0.000265

AC:

AN:

22636

East Asian (EAS)

AF:

0.00

AC:

AN:

35230

South Asian (SAS)

AF:

0.000108

AC:

AN:

73838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47744

Middle Eastern (MID)

AF:

0.00291

AC:

AN:

5502

European-Non Finnish (NFE)

AF:

0.000327

AC:

345

AN:

1056188

Other (OTH)

AF:

0.00395

AC:

222

AN:

56230

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

159

318

478

637

796

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

152

228

304

380

<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:

0.0194

AC:

2955

AN:

152274

Hom.:

100

Cov.:

AF XY:

0.0189

AC XY:

1405

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.0662

AC:

2749

AN:

41556

American (AMR)

AF:

0.00849

AC:

130

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5180

South Asian (SAS)

AF:

0.000415

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000515

AC:

AN:

68002

Other (OTH)

AF:

0.0161

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

145

290

435

580

725

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<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:

0.00335

Hom.:

Bravo

AF:

0.0229

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0723

AC:

100

ESP6500EA

AF:

0.000629

AC:

ExAC

AF:

0.00580

AC:

158

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Glaucoma 1, open angle, F (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.45

CADD

Benign

4.7

(source)

DANN

Uncertain

1.0

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.072

LIST_S2

Benign

0.40

MetaRNN

Benign

0.0022

MetaSVM

Benign

-1.0

PhyloP100

-0.047

PROVEAN

Benign

-1.0

REVEL

Benign

0.072

Sift

Benign

0.092

Sift4G

Benign

0.077

Polyphen

0.0060

Vest4

0.21

MVP

0.22

ClinPred

0.0059

GERP RS

3.7

PromoterAI

0.052

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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