chr21-17570136-A-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

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>T		intron	N/A	NP_001193995.1
	CXADR	NM_001338.5	MANE Select	c.*4444A>T		downstream_gene	N/A	NP_001329.1
	CXADR	NM_001207063.2		c.*4521A>T		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>T		intron	N/A	ENSP00000383033.1
	CXADR	ENST00000284878.12	TSL:1 MANE Select	c.*4444A>T		downstream_gene	N/A	ENSP00000284878.7

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

African (AFR) AF: 0.109 AC: 1727 AN: 15784

American (AMR) AF: 0.0732 AC: 72 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 906 AN: 5152

East Asian (EAS) AF: 0.00110 AC: 4 AN: 3630

South Asian (SAS) AF: 0.0898 AC: 1478 AN: 16460

European-Finnish (FIN) AF: 0.0906 AC: 25 AN: 276

Middle Eastern (MID) AF: 0.137 AC: 222 AN: 1620

European-Non Finnish (NFE) AF: 0.129 AC: 98559 AN: 761792

Other (OTH) AF: 0.121 AC: 3306 AN: 27296

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

African (AFR) AF: 0.109 AC: 4537 AN: 41528

American (AMR) AF: 0.103 AC: 1578 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 634 AN: 3464

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5182

South Asian (SAS) AF: 0.0899 AC: 434 AN: 4826

European-Finnish (FIN) AF: 0.0773 AC: 819 AN: 10596

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8326 AN: 68002

Other (OTH) AF: 0.117 AC: 248 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.41
DANN	Benign	0.84
PhyloP100		-0.66
Mutation Taster		=100/0	polymorphism (auto)

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;