21-17561391-C-T

Variant names:

• chr21-17561391-C-T
• rs201624272
• NM_001338.5:c.748C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001338.5(CXADR):​c.748C>T​(p.Leu250Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,422 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: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CXADR NM_001338.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.18
• 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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP7: Synonymous conserved (PhyloP=3.18 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXADR	NM_001338.5	MANE Select	c.748C>T	p.Leu250Leu	synonymous	Exon 6 of 7	NP_001329.1	P78310-1
	CXADR	NM_001207066.2		c.748C>T	p.Leu250Leu	synonymous	Exon 6 of 8	NP_001193995.1	P78310-6
	CXADR	NM_001207063.2		c.571+2260C>T		intron	N/A	NP_001193992.1	P78310-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXADR	ENST00000284878.12	TSL:1 MANE Select	c.748C>T	p.Leu250Leu	synonymous	Exon 6 of 7	ENSP00000284878.7	P78310-1
	CXADR	ENST00000400166.5	TSL:1	c.571+2260C>T		intron	N/A	ENSP00000383030.1	P78310-5
	CXADR	ENST00000400165.5	TSL:1	c.416-4037C>T		intron	N/A	ENSP00000383029.1	P78310-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459422 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 726032

African (AFR) AF: 0.00 AC: 0 AN: 33408

American (AMR) AF: 0.00 AC: 0 AN: 44572

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26086

East Asian (EAS) AF: 0.00 AC: 0 AN: 39630

South Asian (SAS) AF: 0.00 AC: 0 AN: 85870

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5390

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110824

Other (OTH) AF: 0.00 AC: 0 AN: 60278

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	7.8
DANN	Benign	0.70
PhyloP100		3.2

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: rs201624272; hg19: chr21-18933709; COSMIC: COSV99515625;