Genetic Variant ASB18:p.His407Asn (chr2-236195054-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_212556.4(ASB18):c.1219C>A(p.His407Asn) variant causes a missense change. The variant allele was found at a frequency of 0.121 in 1,605,874 control chromosomes in the GnomAD database, including 12,548 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.13 ( 1445 hom., cov: 33)

Exomes 𝑓: 0.12 ( 11103 hom. )

Consequence

ASB18
NM_212556.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.13

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018608868).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASB18	NM_212556.4 link	c.1219C>A	p.His407Asn	missense_variant	Exon 6 of 6	ENST00000409749.8	NP_997721.2
GBX2-AS1	NR_186035.1 link	n.229-18609G>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASB18	ENST00000409749.8 link	c.1219C>A	p.His407Asn	missense_variant	Exon 6 of 6	1	NM_212556.4	ENSP00000386532.3		Q6ZVZ8-1

Frequencies

GnomAD3 genomes

AF:

0.131

AC:

19920

AN:

152114

Hom.:

1441

Cov.:

show subpopulations

Gnomad AFR

AF:

0.169

Gnomad AMI

AF:

0.192

Gnomad AMR

AF:

0.0811

Gnomad ASJ

AF:

0.118

Gnomad EAS

AF:

0.00250

Gnomad SAS

AF:

0.143

Gnomad FIN

AF:

0.157

Gnomad MID

AF:

0.226

Gnomad NFE

AF:

0.123

Gnomad OTH

AF:

0.145

GnomAD3 exomes

AF:

0.113

AC:

27682

AN:

245254

Hom.:

1799

AF XY:

0.116

AC XY:

15438

AN XY:

132980

show subpopulations

Gnomad AFR exome

AF:

0.169

Gnomad AMR exome

AF:

0.0565

Gnomad ASJ exome

AF:

0.113

Gnomad EAS exome

AF:

0.00156

Gnomad SAS exome

AF:

0.152

Gnomad FIN exome

AF:

0.153

Gnomad NFE exome

AF:

0.122

Gnomad OTH exome

AF:

0.124

GnomAD4 exome

AF:

0.120

AC:

173997

AN:

1453644

Hom.:

11103

Cov.:

AF XY:

0.121

AC XY:

87323

AN XY:

721926

show subpopulations

Gnomad4 AFR exome

AF:

0.166

Gnomad4 AMR exome

AF:

0.0613

Gnomad4 ASJ exome

AF:

0.114

Gnomad4 EAS exome

AF:

0.000835

Gnomad4 SAS exome

AF:

0.158

Gnomad4 FIN exome

AF:

0.156

Gnomad4 NFE exome

AF:

0.120

Gnomad4 OTH exome

AF:

0.121

GnomAD4 genome

AF:

0.131

AC:

19941

AN:

152230

Hom.:

1445

Cov.:

AF XY:

0.130

AC XY:

9693

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.169

Gnomad4 AMR

AF:

0.0810

Gnomad4 ASJ

AF:

0.118

Gnomad4 EAS

AF:

0.00251

Gnomad4 SAS

AF:

0.143

Gnomad4 FIN

AF:

0.157

Gnomad4 NFE

AF:

0.123

Gnomad4 OTH

AF:

0.143

Alfa

AF:

0.118

Hom.:

2098

Bravo

AF:

0.125

TwinsUK

AF:

0.121

AC:

448

ALSPAC

AF:

0.120

AC:

461

ESP6500AA

AF:

0.157

AC:

660

ESP6500EA

AF:

0.114

AC:

970

ExAC

AF:

0.118

AC:

14282

Asia WGS

AF:

0.0810

AC:

281

AN:

3478

EpiCase

AF:

0.117

EpiControl

AF:

0.116

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

.;T

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.67

T;T

MetaRNN

Benign

0.0019

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.5

.;H

PrimateAI

Uncertain

0.53

PROVEAN

Pathogenic

-5.8

.;D

REVEL

Benign

0.19

Sift

Uncertain

0.0030

.;D

Sift4G

Uncertain

0.0050

.;D

Polyphen

0.96

.;D

Vest4

0.26

MPC

0.47

ClinPred

0.047

GERP RS

3.7

Varity_R

0.36

gMVP

0.39

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over