rs381861

Positions:

• chr21-17570136-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001207066.2(CXADR):​c.1017+4525A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 985,188 control chromosomes in the GnomAD database, including 7,880 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.

• Frequency:
  • Genomes: 𝑓 0.11 (971 hom., cov: 32)
  • Exomes 𝑓: 0.13 (6909 hom.)
• Consequence: CXADR NM_001207066.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.663

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CXADR	NM_001338.5			downstream_gene_variant		ENST00000284878.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CXADR	ENST00000400169.1	c.1017+4525A>T		intron_variant		5		A1
CXADR	ENST00000284878.12			downstream_gene_variant		1	NM_001338.5	P2

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16715 AN: 152076 Hom.: 969 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.0886

Gnomad FIN AF: 0.0773

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.118

GnomAD4 exome AF: 0.128 AC: 106299 AN: 832994 Hom.: 6909 Cov.: 32 AF XY: 0.128 AC XY: 49300 AN XY: 384662

Gnomad4 AFR exome AF: 0.109

Gnomad4 AMR exome AF: 0.0732

Gnomad4 ASJ exome AF: 0.176

Gnomad4 EAS exome AF: 0.00110

Gnomad4 SAS exome AF: 0.0898

Gnomad4 FIN exome AF: 0.0906

Gnomad4 NFE exome AF: 0.129

Gnomad4 OTH exome AF: 0.121

GnomAD4 genome AF: 0.110 AC: 16729 AN: 152194 Hom.: 971 Cov.: 32 AF XY: 0.107 AC XY: 7987 AN XY: 74418

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.0899

Gnomad4 FIN AF: 0.0773

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.117

Alfa AF: 0.108 Hom.: 111

Bravo AF: 0.112

Asia WGS AF: 0.0440 AC: 154 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.41
DANN	Benign	0.84

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs381861; hg19: chr21-18942454;