rs2251818

Positions:

• chr21-17532474-C-T

Variant summary

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

The NM_001338.5(CXADR):​c.44-14553C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 152,034 control chromosomes in the GnomAD database, including 26,733 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 0.57 (26733 hom., cov: 32)
• Consequence: CXADR NM_001338.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.560

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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CXADR	NM_001338.5	c.44-14553C>T		intron_variant		ENST00000284878.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CXADR	ENST00000284878.12	c.44-14553C>T		intron_variant		1	NM_001338.5	P2

Frequencies

GnomAD3 genomes AF: 0.574 AC: 87268 AN: 151914 Hom.: 26717 Cov.: 32

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.591

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.609

Gnomad SAS AF: 0.682

Gnomad FIN AF: 0.648

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.674

Gnomad OTH AF: 0.597

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.574 AC: 87317 AN: 152034 Hom.: 26733 Cov.: 32 AF XY: 0.575 AC XY: 42747 AN XY: 74306

Gnomad4 AFR AF: 0.338

Gnomad4 AMR AF: 0.648

Gnomad4 ASJ AF: 0.663

Gnomad4 EAS AF: 0.610

Gnomad4 SAS AF: 0.681

Gnomad4 FIN AF: 0.648

Gnomad4 NFE AF: 0.674

Gnomad4 OTH AF: 0.599

Alfa AF: 0.653 Hom.: 19066

Bravo AF: 0.562

Asia WGS AF: 0.639 AC: 2223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.52
DANN	Benign	0.63

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

Other links and lift over

dbSNP: rs2251818; hg19: chr21-18904792;