rs12034

Variant names:

• chr21-17569905-G-A
• rs12034
• NM_001338.5:c.*4213G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001338.5(CXADR):​c.*4213G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 984,758 control chromosomes in the GnomAD database, including 180,295 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 0.48 (20833 hom., cov: 32)
  • Exomes 𝑓: 0.61 (159462 hom.)
• Consequence: CXADR NM_001338.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.361
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXADR	NM_001338.5	c.*4213G>A		3_prime_UTR_variant	Exon 7 of 7	ENST00000284878.12	NP_001329.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXADR	ENST00000284878.12	c.*4213G>A		3_prime_UTR_variant	Exon 7 of 7	1	NM_001338.5	ENSP00000284878.7
CXADR	ENST00000400169.1	c.1017+4294G>A		intron_variant	Intron 7 of 7	5		ENSP00000383033.1

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72459 AN: 151866 Hom.: 20828 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.567

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.520

GnomAD4 exome AF: 0.614 AC: 510981 AN: 832776 Hom.: 159462 Cov.: 32 AF XY: 0.614 AC XY: 236091 AN XY: 384580

African (AFR) AF: 0.0817 AC: 1290 AN: 15786

American (AMR) AF: 0.657 AC: 646 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 2908 AN: 5148

East Asian (EAS) AF: 0.504 AC: 1829 AN: 3628

South Asian (SAS) AF: 0.550 AC: 9046 AN: 16444

European-Finnish (FIN) AF: 0.583 AC: 161 AN: 276

Middle Eastern (MID) AF: 0.565 AC: 915 AN: 1620

European-Non Finnish (NFE) AF: 0.628 AC: 478421 AN: 761602

Other (OTH) AF: 0.578 AC: 15765 AN: 27288

GnomAD4 genome AF: 0.477 AC: 72473 AN: 151982 Hom.: 20833 Cov.: 32 AF XY: 0.477 AC XY: 35401 AN XY: 74276

African (AFR) AF: 0.132 AC: 5470 AN: 41458

American (AMR) AF: 0.595 AC: 9084 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.569 AC: 1974 AN: 3468

East Asian (EAS) AF: 0.523 AC: 2690 AN: 5148

South Asian (SAS) AF: 0.540 AC: 2602 AN: 4820

European-Finnish (FIN) AF: 0.559 AC: 5896 AN: 10546

Middle Eastern (MID) AF: 0.568 AC: 166 AN: 292

European-Non Finnish (NFE) AF: 0.633 AC: 43019 AN: 67948

Other (OTH) AF: 0.524 AC: 1106 AN: 2112

Alfa AF: 0.557 Hom.: 4111

Bravo AF: 0.462

Asia WGS AF: 0.534 AC: 1856 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	7.3
DANN	Benign	0.75
PhyloP100		0.36
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12034; hg19: chr21-18942223;