chr21-17517899-G-A

Variant names:

• chr21-17517899-G-A
• rs211953
• NM_001338.5:c.43+4727G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001338.5(CXADR):​c.43+4727G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,134 control chromosomes in the GnomAD database, including 1,850 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 0.14 (1850 hom., cov: 32)
• Consequence: CXADR NM_001338.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.270
• Publications: 7 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]

BTF3L4P1 (HGNC:39645): (basic transcription factor 3 like 4 pseudogene 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001338.5. 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_001338.5	MANE Select	c.43+4727G>A		intron	N/A	NP_001329.1
	CXADR	NM_001207066.2		c.43+4727G>A		intron	N/A	NP_001193995.1
	CXADR	NM_001207063.2		c.43+4727G>A		intron	N/A	NP_001193992.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXADR	ENST00000284878.12	TSL:1 MANE Select	c.43+4727G>A		intron	N/A	ENSP00000284878.7
	CXADR	ENST00000400166.5	TSL:1	c.43+4727G>A		intron	N/A	ENSP00000383030.1
	CXADR	ENST00000400165.5	TSL:1	c.43+4727G>A		intron	N/A	ENSP00000383029.1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21875 AN: 152016 Hom.: 1845 Cov.: 32

Gnomad AFR AF: 0.0823

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.0323

Gnomad SAS AF: 0.0715

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.136

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

GnomAD4 genome AF: 0.144 AC: 21900 AN: 152134 Hom.: 1850 Cov.: 32 AF XY: 0.139 AC XY: 10340 AN XY: 74350

African (AFR) AF: 0.0826 AC: 3432 AN: 41530

American (AMR) AF: 0.116 AC: 1766 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 683 AN: 3468

East Asian (EAS) AF: 0.0323 AC: 167 AN: 5166

South Asian (SAS) AF: 0.0726 AC: 350 AN: 4822

European-Finnish (FIN) AF: 0.157 AC: 1655 AN: 10568

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.196 AC: 13359 AN: 67992

Other (OTH) AF: 0.134 AC: 284 AN: 2114

Alfa AF: 0.178 Hom.: 11338

Bravo AF: 0.139

Asia WGS AF: 0.0560 AC: 196 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	14
DANN	Benign	0.83
PhyloP100		-0.27
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: rs211953; hg19: chr21-18890217;