chr21-17570136-A-G

Variant names:

• chr21-17570136-A-G
• rs381861
• NM_001207066.2:c.1017+4525A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001207066.2(CXADR):​c.1017+4525A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000012 in 833,086 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000012 (0 hom.)
• Consequence: CXADR NM_001207066.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.663
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001207066.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXADR	NM_001207066.2		c.1017+4525A>G		intron	N/A	NP_001193995.1
	CXADR	NM_001338.5	MANE Select	c.*4444A>G		downstream_gene	N/A	NP_001329.1
	CXADR	NM_001207063.2		c.*4521A>G		downstream_gene	N/A	NP_001193992.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXADR	ENST00000400169.1	TSL:5	c.1017+4525A>G		intron	N/A	ENSP00000383033.1
	CXADR	ENST00000284878.12	TSL:1 MANE Select	c.*4444A>G		downstream_gene	N/A	ENSP00000284878.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000120 AC: 1 AN: 833086 Hom.: 0 Cov.: 32 AF XY: 0.00000260 AC XY: 1 AN XY: 384698

African (AFR) AF: 0.00 AC: 0 AN: 15786

American (AMR) AF: 0.00 AC: 0 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5152

East Asian (EAS) AF: 0.00 AC: 0 AN: 3630

South Asian (SAS) AF: 0.0000608 AC: 1 AN: 16460

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 276

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1620

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 761880

Other (OTH) AF: 0.00 AC: 0 AN: 27298

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.69
DANN	Benign	0.78
PhyloP100		-0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

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

Other links and lift over

dbSNP: rs381861; hg19: chr21-18942454;