Genetic Variant ASB18:p.Gly283Arg (chr2-236214616-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_212556.4(ASB18):c.847G>A(p.Gly283Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000306 in 1,208,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00032 ( 0 hom. )

Consequence

ASB18
NM_212556.4 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:2

Conservation

PhyloP100: 6.61

Publications

2 publications found

Variant links:

Genes affected

ASB18 (HGNC:19770): (ankyrin repeat and SOCS box containing 18) The protein encoded by this gene is a member of the ankyrin repeat and SOCS box-containing (ASB) family of proteins. They contain ankyrin repeat sequence and a SOCS box domain. The SOCS box serves to couple suppressor of cytokine signalling (SOCS) proteins and their binding partners with the elongin B and C complex, possibly targeting them for degradation. [provided by RefSeq, Feb 2017]

ASB18 links:

GBX2-AS1 (HGNC:55714): (GBX2 and ASB18 antisense RNA 1)

GBX2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.793

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_212556.4. 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
	ASB18	NM_212556.4	MANE Select	c.847G>A	p.Gly283Arg	missense	Exon 4 of 6	NP_997721.2	Q6ZVZ8-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ASB18	ENST00000409749.8	TSL:1 MANE Select	c.847G>A	p.Gly283Arg	missense	Exon 4 of 6	ENSP00000386532.3	Q6ZVZ8-1
ASB18	ENST00000645891.1		c.760G>A	p.Gly254Arg	missense	Exon 3 of 5	ENSP00000496134.1	Q6ZVZ8-2
GBX2-AS1	ENST00000415226.1	TSL:4	n.224-44891C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000214

AC:

AN:

149216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000668

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:

0.000463

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

470

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000319

AC:

338

AN:

1059688

Hom.:

Cov.:

AF XY:

0.000337

AC XY:

170

AN XY:

504354

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

20980

American (AMR)

AF:

0.000730

AC:

AN:

6854

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12150

East Asian (EAS)

AF:

0.00

AC:

AN:

21654

South Asian (SAS)

AF:

0.0000401

AC:

AN:

24956

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21220

Middle Eastern (MID)

AF:

0.00112

AC:

AN:

2676

European-Non Finnish (NFE)

AF:

0.000350

AC:

318

AN:

908068

Other (OTH)

AF:

0.000267

AC:

AN:

41130

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

103

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.000214

AC:

AN:

149216

Hom.:

Cov.:

AF XY:

0.000220

AC XY:

AN XY:

72738

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41122

American (AMR)

AF:

0.0000668

AC:

AN:

14976

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3422

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9462

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000463

AC:

AN:

66962

Other (OTH)

AF:

0.00

AC:

AN:

2052

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

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:

0.000285

Hom.:

Bravo

AF:

0.000261

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Uncertain

0.034

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.81

M_CAP

Pathogenic

0.79

MetaRNN

Pathogenic

0.79

MetaSVM

Uncertain

-0.0083

MutationAssessor

Uncertain

2.7

PhyloP100

6.6

PrimateAI

Pathogenic

0.92

PROVEAN

Pathogenic

-5.1

REVEL

Uncertain

0.38

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0050

Polyphen

1.0

Vest4

0.57

MutPred

0.43

Gain of MoRF binding (P = 0.044)

MVP

0.72

MPC

1.8

ClinPred

0.99

GERP RS

3.7

PromoterAI

0.019

Neutral

(source)

Varity_R

0.38

gMVP

0.42

Mutation Taster

=62/38

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