dbSNP rs104886485: ASB10:p.Leu366Phe (chr7-151180947-G-A) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_ModerateBS2_Supporting

The NM_001142459.2(ASB10):c.1096C>T(p.Leu366Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000147 in 1,533,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

ASB10
NM_001142459.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1O:1

Conservation

PhyloP100: 4.09

Publications

0 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: Likely_benign. The variant received -3 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.19658491).

BS2

High AC in GnomAd4 at 10 Unknown,AD 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	HGVSp	Effect	Exon Rank	Protein	UniProt
ASB10	NM_001142459.2	MANE Select	c.1096C>T	p.Leu366Phe	missense	Exon 3 of 6	NP_001135931.2	Q8WXI3-1
ASB10	NM_080871.4		c.1051C>T	p.Leu351Phe	missense	Exon 3 of 6	NP_543147.2	Q8WXI3-3
ASB10	NM_001142460.1		c.1096C>T	p.Leu366Phe	missense	Exon 3 of 5	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.1096C>T	p.Leu366Phe	missense	Exon 3 of 6	ENSP00000391137.2	Q8WXI3-1
ASB10	ENST00000275838.5	TSL:1	c.1096C>T	p.Leu366Phe	missense	Exon 3 of 5	ENSP00000275838.1	Q8WXI3-2
ASB10	ENST00000968508.1		c.1096C>T	p.Leu366Phe	missense	Exon 3 of 6	ENSP00000638567.1

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.000132

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000729

AC:

AN:

178420

AF XY:

0.0000814

show subpopulations

Gnomad AFR exome

AF:

0.000164

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000138

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000156

AC:

216

AN:

1380846

Hom.:

Cov.:

AF XY:

0.000158

AC XY:

107

AN XY:

677156

show subpopulations

African (AFR)

AF:

0.0000952

AC:

AN:

31528

American (AMR)

AF:

0.00

AC:

AN:

35680

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22038

East Asian (EAS)

AF:

0.00

AC:

AN:

38028

South Asian (SAS)

AF:

0.00

AC:

AN:

76856

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47134

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4248

European-Non Finnish (NFE)

AF:

0.000197

AC:

211

AN:

1068686

Other (OTH)

AF:

0.0000353

AC:

AN:

56648

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

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:

0.0000657

AC:

AN:

152258

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41468

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

68048

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

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:

0.0000606

Hom.:

Bravo

AF:

0.0000756

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000334

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Glaucoma 1, open angle, F (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.50

BayesDel_addAF

Benign

-0.077

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.011

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.76

M_CAP

Benign

0.031

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.66

MutationAssessor

Benign

0.97

PhyloP100

4.1

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.19

REVEL

Benign

0.26

Sift

Benign

0.45

Sift4G

Benign

0.16

Polyphen

1.0

Vest4

0.36

MVP

0.54

MPC

0.12

ClinPred

0.13

GERP RS

5.1

Varity_R

0.13

gMVP

0.51

Mutation Taster

=40/60

disease causing

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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