rs2251818

Variant names:

• chr21-17532474-C-T
• rs2251818
• NM_001338.5:c.44-14553C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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 (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 rank	MANE	Protein	UniProt
CXADR	NM_001338.5	c.44-14553C>T		intron_variant	Intron 1 of 6	ENST00000284878.12	NP_001329.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXADR	ENST00000284878.12	c.44-14553C>T		intron_variant	Intron 1 of 6	1	NM_001338.5	ENSP00000284878.7

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

African (AFR) AF: 0.338 AC: 14016 AN: 41452

American (AMR) AF: 0.648 AC: 9900 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.663 AC: 2302 AN: 3470

East Asian (EAS) AF: 0.610 AC: 3144 AN: 5158

South Asian (SAS) AF: 0.681 AC: 3281 AN: 4818

European-Finnish (FIN) AF: 0.648 AC: 6838 AN: 10556

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.674 AC: 45839 AN: 67994

Other (OTH) AF: 0.599 AC: 1264 AN: 2110

Alfa AF: 0.648 Hom.: 25152

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
PhyloP100		-0.56
Mutation Taster		=100/0	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: rs2251818; hg19: chr21-18904792;