Variant chr21-17565577-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001338.5(CXADR):c.983G>A(p.Arg328His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00127 in 1,613,452 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00080 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0013 ( 2 hom. )

Consequence

CXADR
NM_001338.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.51

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007686883).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CXADR	NM_001338.5 linkuse as main transcript	c.983G>A	p.Arg328His	missense_variant	7/7	ENST00000284878.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CXADR	ENST00000284878.12 linkuse as main transcript	c.983G>A	p.Arg328His	missense_variant	7/7	1	NM_001338.5	P2	P78310-1
CXADR	ENST00000400166.5 linkuse as main transcript	c.721G>A	p.Ala241Thr	missense_variant	5/5	1			P78310-5
CXADR	ENST00000400165.5 linkuse as main transcript	c.565G>A	p.Ala189Thr	missense_variant	4/4	1			P78310-4
CXADR	ENST00000400169.1 linkuse as main transcript	c.983G>A	p.Arg328His	missense_variant	7/8	5		A1	P78310-6

Frequencies

GnomAD3 genomes

AF:

0.000803

AC:

122

AN:

151976

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000218

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000853

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00193

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00110

Gnomad OTH

AF:

0.00384

GnomAD3 exomes

AF:

0.000968

AC:

243

AN:

251134

Hom.:

AF XY:

0.00111

AC XY:

151

AN XY:

135718

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000665

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00245

Gnomad SAS exome

AF:

0.00144

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.00106

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.00132

AC:

1934

AN:

1461358

Hom.:

Cov.:

AF XY:

0.00139

AC XY:

1012

AN XY:

727004

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.000626

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00123

Gnomad4 SAS exome

AF:

0.00151

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.00145

Gnomad4 OTH exome

AF:

0.00144

GnomAD4 genome

AF:

0.000802

AC:

122

AN:

152094

Hom.:

Cov.:

AF XY:

0.000928

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.000852

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00194

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00110

Gnomad4 OTH

AF:

0.00380

Alfa

AF:

0.00141

Hom.:

Bravo

AF:

0.000876

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.00101

AC:

123

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 10, 2023

The c.983G>A (p.R328H) alteration is located in exon 7 (coding exon 7) of the CXADR gene. This alteration results from a G to A substitution at nucleotide position 983, causing the arginine (R) at amino acid position 328 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.046

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.97

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.40

T;T

M_CAP

Benign

0.039

MetaRNN

Benign

0.0077

T;T

MetaSVM

Benign

-0.55

MutationTaster

Benign

0.98

D;D;D;N;N

PROVEAN

Benign

-0.080

N;N

REVEL

Benign

0.18

Sift

Benign

0.040

D;D

Sift4G

Pathogenic

0.0

.;D

Polyphen

0.0080

B;B

Vest4

0.13

MVP

0.92

ClinPred

0.012

GERP RS

0.80

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over