Genetic Variant ASB10:p.Arg378Trp (chr7-151176649-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001142459.2(ASB10):c.1132C>T(p.Arg378Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.001 in 1,551,398 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00099 ( 14 hom. )

Consequence

ASB10
NM_001142459.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.50

Publications

6 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: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen

ASB10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008231372).

BP6

Variant 7-151176649-G-A is Benign according to our data. Variant chr7-151176649-G-A is described in ClinVar as Benign. ClinVar VariationId is 728668.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00112 (171/152254) while in subpopulation EAS AF = 0.0286 (148/5170). AF 95% confidence interval is 0.0249. There are 3 homozygotes in GnomAd4. There are 96 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 171 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	UniProt
ASB10	NM_001142459.2	MANE Select	c.1132C>T	p.Arg378Trp	missense	Exon 4 of 6	NP_001135931.2	Q8WXI3-1
ASB10	NM_080871.4		c.1087C>T	p.Arg363Trp	missense	Exon 4 of 6	NP_543147.2	Q8WXI3-3
ASB10	NM_001142460.1		c.1105-352C>T		intron	N/A	NP_001135932.2	Q8WXI3-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ASB10	ENST00000420175.3	TSL:1 MANE Select	c.1132C>T	p.Arg378Trp	missense	Exon 4 of 6	ENSP00000391137.2	Q8WXI3-1
ASB10	ENST00000275838.5	TSL:1	c.1105-352C>T		intron	N/A	ENSP00000275838.1	Q8WXI3-2
ASB10	ENST00000968508.1		c.1132C>T	p.Arg378Trp	missense	Exon 4 of 6	ENSP00000638567.1

Frequencies

GnomAD3 genomes

AF:

0.00112

AC:

171

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0286

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.00239

AC:

376

AN:

157036

AF XY:

0.00232

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000405

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0335

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000328

Gnomad OTH exome

AF:

0.000677

GnomAD4 exome

AF:

0.000990

AC:

1385

AN:

1399144

Hom.:

Cov.:

AF XY:

0.000987

AC XY:

681

AN XY:

690020

show subpopulations

African (AFR)

AF:

0.000222

AC:

AN:

31596

American (AMR)

AF:

0.0000280

AC:

AN:

35700

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25180

East Asian (EAS)

AF:

0.0350

AC:

1252

AN:

35734

South Asian (SAS)

AF:

0.000593

AC:

AN:

79236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49074

Middle Eastern (MID)

AF:

0.000176

AC:

AN:

5696

European-Non Finnish (NFE)

AF:

0.0000139

AC:

AN:

1078898

Other (OTH)

AF:

0.00107

AC:

AN:

58030

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

155

233

310

388

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

<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:

0.00112

AC:

171

AN:

152254

Hom.:

Cov.:

AF XY:

0.00129

AC XY:

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.000241

AC:

AN:

41532

American (AMR)

AF:

0.000196

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.0286

AC:

148

AN:

5170

South Asian (SAS)

AF:

0.00104

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68026

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.000243

Hom.:

Bravo

AF:

0.00135

ExAC

AF:

0.000742

AC:

Asia WGS

AF:

0.00693

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

ASB10-related disorder (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

Eigen

Benign

-0.032

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.70

LIST_S2

Uncertain

0.94

MetaRNN

Benign

0.0082

MetaSVM

Benign

-0.52

MutationAssessor

Uncertain

2.3

PhyloP100

1.5

PrimateAI

Benign

0.36

PROVEAN

Pathogenic

-4.5

REVEL

Uncertain

0.49

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.0060

Polyphen

1.0

Vest4

0.58

MVP

0.73

MPC

0.27

ClinPred

0.13

GERP RS

1.0

Varity_R

0.35

gMVP

0.55

Mutation Taster

=81/19

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

Computational scores

Splicing

Publications

Other links and lift over