ENST00000400166.5:c.584A>G

Variant names:

• chr21-17565440-A-G
• rs437470
• ENST00000400166.5:c.584A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000400166.5(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. 13/17 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 ENST00000400166.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.73
• Publications: 14 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000400166.5. 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
	CXADR	NM_001338.5	MANE Select	c.846A>G	p.Pro282Pro	synonymous	Exon 7 of 7	NP_001329.1	P78310-1
	CXADR	NM_001207063.2		c.584A>G	p.His195Arg	missense	Exon 5 of 5	NP_001193992.1	P78310-5
	CXADR	NM_001207064.2		c.428A>G	p.His143Arg	missense	Exon 4 of 4	NP_001193993.1	P78310-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXADR	ENST00000400166.5	TSL:1	c.584A>G	p.His195Arg	missense	Exon 5 of 5	ENSP00000383030.1	P78310-5
	CXADR	ENST00000400165.5	TSL:1	c.428A>G	p.His143Arg	missense	Exon 4 of 4	ENSP00000383029.1	P78310-4
	CXADR	ENST00000356275.10	TSL:1	c.223A>G	p.Thr75Ala	missense	Exon 3 of 3	ENSP00000348620.6	P78310-3

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27079 AN: 151902 Hom.: 3053 Cov.: 31

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

GnomAD2 exomes AF: 0.133 AC: 33451 AN: 250738 AF XY: 0.131

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 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.: 33 AF XY: 0.130 AC XY: 94541 AN XY: 726898

African (AFR) AF: 0.330 AC: 11057 AN: 33464

American (AMR) AF: 0.0890 AC: 3978 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 4612 AN: 26106

East Asian (EAS) AF: 0.164 AC: 6503 AN: 39692

South Asian (SAS) AF: 0.106 AC: 9146 AN: 86230

European-Finnish (FIN) AF: 0.0814 AC: 4346 AN: 53414

Middle Eastern (MID) AF: 0.147 AC: 845 AN: 5760

European-Non Finnish (NFE) AF: 0.128 AC: 142496 AN: 1111504

Other (OTH) AF: 0.143 AC: 8649 AN: 60368

GnomAD4 genome AF: 0.178 AC: 27128 AN: 152020 Hom.: 3064 Cov.: 31 AF XY: 0.176 AC XY: 13059 AN XY: 74336

African (AFR) AF: 0.322 AC: 13349 AN: 41408

American (AMR) AF: 0.132 AC: 2023 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 634 AN: 3472

East Asian (EAS) AF: 0.161 AC: 832 AN: 5176

South Asian (SAS) AF: 0.114 AC: 550 AN: 4818

European-Finnish (FIN) AF: 0.0778 AC: 823 AN: 10584

Middle Eastern (MID) AF: 0.161 AC: 47 AN: 292

European-Non Finnish (NFE) AF: 0.124 AC: 8402 AN: 67974

Other (OTH) AF: 0.175 AC: 369 AN: 2110

Alfa AF: 0.142 Hom.: 6878

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.30	T
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	N
LIST_S2	Benign	0.23	T
MetaRNN	Benign	0.0012	T
MetaSVM	Benign	-1.1	T
PhyloP100		-2.7
PROVEAN	Benign	-0.87	N
REVEL	Benign	0.23
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.026	D
Polyphen		0.0	B
Vest4		0.047
ClinPred		0.0079	T
GERP RS		-11
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=94/6	polymorphism (auto)

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

Other links and lift over

dbSNP: rs437470; hg19: chr21-18937758; COSMIC: COSV107325639;