Genetic Variant ASB18:p.Glu291Gln (chr2-236214592-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_212556.4(ASB18):c.871G>C(p.Glu291Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000134 in 1,265,428 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

ASB18
NM_212556.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.275

Publications

0 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: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11869034).

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.871G>C	p.Glu291Gln	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.871G>C	p.Glu291Gln	missense	Exon 4 of 6	ENSP00000386532.3	Q6ZVZ8-1
ASB18	ENST00000645891.1		c.784G>C	p.Glu262Gln	missense	Exon 3 of 5	ENSP00000496134.1	Q6ZVZ8-2
ASB18	ENST00000447030.1	TSL:4	c.10G>C	p.Glu4Gln	missense	Exon 1 of 2	ENSP00000411434.1	H7C3E8

Frequencies

GnomAD3 genomes

AF:

0.00000666

AC:

AN:

150046

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

522

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ 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:

0.0000143

AC:

AN:

1115382

Hom.:

Cov.:

AF XY:

0.0000243

AC XY:

AN XY:

534080

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22076

American (AMR)

AF:

0.00

AC:

AN:

7852

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13954

East Asian (EAS)

AF:

0.00

AC:

AN:

24580

South Asian (SAS)

AF:

0.000368

AC:

AN:

32596

European-Finnish (FIN)

AF:

0.00

AC:

AN:

24510

Middle Eastern (MID)

AF:

0.000337

AC:

AN:

2966

European-Non Finnish (NFE)

AF:

0.00000212

AC:

AN:

942322

Other (OTH)

AF:

0.0000225

AC:

AN:

44526

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

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:

0.00000666

AC:

AN:

150046

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

73194

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41188

American (AMR)

AF:

0.00

AC:

AN:

15046

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3442

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.000207

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9744

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67358

Other (OTH)

AF:

0.00

AC:

AN:

2062

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

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:

0.00

Hom.:

Bravo

AF:

0.00000378

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

0.16

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.020

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.076

LIST_S2

Benign

0.52

M_CAP

Pathogenic

0.53

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.33

PhyloP100

0.28

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

0.040

REVEL

Benign

0.082

Sift

Benign

0.78

Sift4G

Benign

0.69

Polyphen

0.48

Vest4

0.066

MutPred

0.14

Loss of glycosylation at S295 (P = 0.2235)

MVP

0.27

MPC

1.5

ClinPred

0.48

GERP RS

3.8

PromoterAI

-0.018

Neutral

(source)

Varity_R

0.12

gMVP

0.22

Mutation Taster

=84/16

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

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