Genetic Variant ASB2:p.Ala518Thr (chr14-93939173-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001202429.2(ASB2):c.1552G>A(p.Ala518Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000902 in 1,574,532 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00049 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000048 ( 0 hom. )

Consequence

ASB2
NM_001202429.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0130

Publications

1 publications found

Variant links:

Genes affected

ASB2 (HGNC:16012): (ankyrin repeat and SOCS box containing 2) This gene encodes a member of the ankyrin repeat and SOCS box-containing (ASB) protein family. These proteins play a role in protein degradation by coupling suppressor of cytokine signalling (SOCS) proteins with the elongin BC complex. The encoded protein is a subunit of a multimeric E3 ubiquitin ligase complex that mediates the degradation of actin-binding proteins. This gene plays a role in retinoic acid-induced growth inhibition and differentiation of myeloid leukemia cells. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2011]

ASB2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0048982203).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001202429.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB2	NM_001202429.2	MANE Select	c.1552G>A	p.Ala518Thr	missense	Exon 8 of 10	NP_001189358.1	Q96Q27-2
	ASB2	NM_016150.5		c.1408G>A	p.Ala470Thr	missense	Exon 6 of 8	NP_057234.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ASB2	ENST00000555019.6	TSL:1 MANE Select	c.1552G>A	p.Ala518Thr	missense	Exon 8 of 10	ENSP00000451575.1	Q96Q27-2
ASB2	ENST00000315988.8	TSL:1	c.1408G>A	p.Ala470Thr	missense	Exon 6 of 8	ENSP00000320675.4	Q96Q27-1
ASB2	ENST00000968954.1		c.1627G>A	p.Ala543Thr	missense	Exon 8 of 10	ENSP00000639013.1

Frequencies

GnomAD3 genomes

AF:

0.000486

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.00

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000136

AC:

AN:

205628

AF XY:

0.000124

show subpopulations

Gnomad AFR exome

AF:

0.00195

Gnomad AMR exome

AF:

0.000127

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000478

AC:

AN:

1422200

Hom.:

Cov.:

AF XY:

0.0000455

AC XY:

AN XY:

702760

show subpopulations

African (AFR)

AF:

0.00155

AC:

AN:

32840

American (AMR)

AF:

0.000119

AC:

AN:

41958

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25290

East Asian (EAS)

AF:

0.00

AC:

AN:

38464

South Asian (SAS)

AF:

0.0000118

AC:

AN:

84926

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49658

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5494

European-Non Finnish (NFE)

AF:

0.00000184

AC:

AN:

1085200

Other (OTH)

AF:

0.000154

AC:

AN:

58370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

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:

0.000486

AC:

AN:

152332

Hom.:

Cov.:

AF XY:

0.000470

AC XY:

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.00168

AC:

AN:

41584

American (AMR)

AF:

0.000196

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68022

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

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:

0.000498

Hom.:

Bravo

AF:

0.000567

ESP6500AA

AF:

0.00120

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000184

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.018

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.17

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.0049

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.14

PhyloP100

0.013

PrimateAI

Benign

0.41

PROVEAN

Benign

0.41

REVEL

Benign

0.062

Sift

Benign

0.51

Sift4G

Benign

0.56

Polyphen

0.0

Vest4

0.091

MVP

0.42

MPC

0.18

ClinPred

0.0079

GERP RS

3.0

Varity_R

0.065

gMVP

0.51

Mutation Taster

=97/3

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