Genetic Variant ASB16:p.Arg37Trp (chr17-44170898-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_080863.5(ASB16):c.109C>T(p.Arg37Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000453 in 1,612,012 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R37Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000043 ( 0 hom. )

Consequence

ASB16
NM_080863.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.420

Publications

0 publications found

Variant links:

Genes affected

ASB16 (HGNC:19768): (ankyrin repeat and SOCS box containing 16) 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, Jul 2008]

ASB16 links:

ASB16-AS1 (HGNC:25442): (ASB16 antisense RNA 1)

ASB16-AS1 links:

Genome browser will be placed here

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=0.06625724).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080863.5. 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
	ASB16	NM_080863.5	MANE Select	c.109C>T	p.Arg37Trp	missense	Exon 1 of 5	NP_543139.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ASB16	ENST00000293414.6	TSL:1 MANE Select	c.109C>T	p.Arg37Trp	missense	Exon 1 of 5	ENSP00000293414.1	Q96NS5
ASB16	ENST00000589618.1	TSL:1	n.109C>T		non_coding_transcript_exon	Exon 1 of 5	ENSP00000466033.1	K7ELE0
ASB16	ENST00000591700.1	TSL:4	c.-144C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 3	ENSP00000466349.1	K7EM41

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000614

AC:

AN:

244244

AF XY:

0.0000525

show subpopulations

Gnomad AFR exome

AF:

0.000132

Gnomad AMR exome

AF:

0.000146

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000112

Gnomad FIN exome

AF:

0.0000469

Gnomad NFE exome

AF:

0.0000458

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000432

AC:

AN:

1459738

Hom.:

Cov.:

AF XY:

0.0000303

AC XY:

AN XY:

726160

show subpopulations

African (AFR)

AF:

0.000538

AC:

AN:

33448

American (AMR)

AF:

0.000134

AC:

AN:

44678

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26104

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39660

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86172

European-Finnish (FIN)

AF:

0.0000191

AC:

AN:

52336

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5410

European-Non Finnish (NFE)

AF:

0.0000270

AC:

AN:

1111678

Other (OTH)

AF:

0.0000830

AC:

AN:

60252

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

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:

152274

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.000192

AC:

AN:

41560

American (AMR)

AF:

0.0000654

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68010

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

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:

0.000226

Hom.:

Bravo

AF:

0.000128

ExAC

AF:

0.0000247

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

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

0.087

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.75

M_CAP

Benign

0.018

MetaRNN

Benign

0.066

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

PhyloP100

-0.42

PrimateAI

Benign

0.35

PROVEAN

Benign

-2.0

REVEL

Benign

0.18

Sift

Benign

0.081

Sift4G

Benign

0.14

Polyphen

0.0030

Vest4

0.23

MVP

0.55

MPC

0.58

ClinPred

0.054

GERP RS

2.0

PromoterAI

-0.047

Neutral

(source)

Varity_R

0.11

gMVP

0.51

Mutation Taster

=95/5

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