dbSNP rs437470: CXADR:p.His195Arg (chr21-17565440-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001207063.2(CXADR):c.584A>G(p.His195Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 1,613,248 control chromosomes in the GnomAD database, including 16,884 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.18 ( 3064 hom., cov: 31)

Exomes 𝑓: 0.13 ( 13820 hom. )

Consequence

CXADR
NM_001207063.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.73

Variant links:

Genes affected

CXADR (HGNC:2559): (CXADR Ig-like cell adhesion molecule) The protein encoded by this gene is a type I membrane receptor for group B coxsackieviruses and subgroup C adenoviruses. Several transcript variants encoding different isoforms have been found for this gene. Pseudogenes of this gene are found on chromosomes 15, 18, and 21. [provided by RefSeq, May 2011]

CXADR 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=0.0011855066).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXADR	NM_001338.5 link	c.846A>G	p.Pro282Pro	synonymous_variant	Exon 7 of 7	ENST00000284878.12	NP_001329.1	P78310-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXADR	ENST00000284878.12 link	c.846A>G	p.Pro282Pro	synonymous_variant	Exon 7 of 7	1	NM_001338.5	ENSP00000284878.7		P78310-1

Frequencies

GnomAD3 genomes

AF:

0.178

AC:

27079

AN:

151902

Hom.:

3053

Cov.:

show subpopulations

Gnomad AFR

AF:

0.322

Gnomad AMI

AF:

0.109

Gnomad AMR

AF:

0.133

Gnomad ASJ

AF:

0.183

Gnomad EAS

AF:

0.161

Gnomad SAS

AF:

0.113

Gnomad FIN

AF:

0.0778

Gnomad MID

AF:

0.166

Gnomad NFE

AF:

0.124

Gnomad OTH

AF:

0.175

GnomAD3 exomes

AF:

0.133

AC:

33451

AN:

250738

Hom.:

2719

AF XY:

0.131

AC XY:

17701

AN XY:

135496

show subpopulations

Gnomad AFR exome

AF:

0.326

Gnomad AMR exome

AF:

0.0834

Gnomad ASJ exome

AF:

0.180

Gnomad EAS exome

AF:

0.174

Gnomad SAS exome

AF:

0.107

Gnomad FIN exome

AF:

0.0784

Gnomad NFE exome

AF:

0.128

Gnomad OTH exome

AF:

0.129

GnomAD4 exome

AF:

0.131

AC:

191632

AN:

1461228

Hom.:

13820

Cov.:

AF XY:

0.130

AC XY:

94541

AN XY:

726898

show subpopulations

Gnomad4 AFR exome

AF:

0.330

Gnomad4 AMR exome

AF:

0.0890

Gnomad4 ASJ exome

AF:

0.177

Gnomad4 EAS exome

AF:

0.164

Gnomad4 SAS exome

AF:

0.106

Gnomad4 FIN exome

AF:

0.0814

Gnomad4 NFE exome

AF:

0.128

Gnomad4 OTH exome

AF:

0.143

GnomAD4 genome

AF:

0.178

AC:

27128

AN:

152020

Hom.:

3064

Cov.:

AF XY:

0.176

AC XY:

13059

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.322

Gnomad4 AMR

AF:

0.132

Gnomad4 ASJ

AF:

0.183

Gnomad4 EAS

AF:

0.161

Gnomad4 SAS

AF:

0.114

Gnomad4 FIN

AF:

0.0778

Gnomad4 NFE

AF:

0.124

Gnomad4 OTH

AF:

0.175

Alfa

AF:

0.137

Hom.:

3176

Bravo

AF:

0.190

TwinsUK

AF:

0.128

AC:

476

ALSPAC

AF:

0.133

AC:

514

ESP6500AA

AF:

0.319

AC:

1405

ESP6500EA

AF:

0.125

AC:

1079

ExAC

AF:

0.139

AC:

16856

Asia WGS

AF:

0.122

AC:

427

AN:

3478

EpiCase

AF:

0.134

EpiControl

AF:

0.136

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Uncertain

-0.060

CADD

Benign

0.91

DANN

Benign

0.32

Eigen

Benign

-2.4

Eigen_PC

Benign

-2.5

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.23

T;T

MetaRNN

Benign

0.0012

T;T

MetaSVM

Benign

-1.1

PROVEAN

Benign

-0.87

N;N

REVEL

Benign

0.23

Sift

Pathogenic

0.0

D;T

Sift4G

Uncertain

0.026

D;T

Polyphen

0.0

B;B

Vest4

0.047

ClinPred

0.0079

GERP RS

-11

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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