11-616865-G-T

Variant names:

• chr11-616865-G-T
• rs3758650
• NM_021924.5:c.*486C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021924.5(CDHR5):​c.*486C>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 0.0000373 in 26,776 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: 0.000037 (0 hom.)
• Consequence: CDHR5 NM_021924.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.693
• Publications: 25 publications found

Genes affected

CDHR5 (HGNC:7521): (cadherin related family member 5) This gene is a novel mucin-like gene that is a member of the cadherin superfamily. While encoding nonpolymorphic tandem repeats rich in proline, serine and threonine similar to mucin proteins, the gene also contains sequence encoding calcium-binding motifs found in all cadherins. The role of the hybrid extracellular region and the specific function of this protein have not yet been determined. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jan 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.022).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021924.5. 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
	CDHR5	NM_021924.5	MANE Select	c.*486C>A		3_prime_UTR	Exon 15 of 15	NP_068743.3
	CDHR5	NM_001171968.3		c.*486C>A		3_prime_UTR	Exon 15 of 15	NP_001165439.2
	CDHR5	NM_031264.5		c.*486C>A		3_prime_UTR	Exon 14 of 14	NP_112554.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDHR5	ENST00000397542.7	TSL:1 MANE Select	c.*486C>A		3_prime_UTR	Exon 15 of 15	ENSP00000380676.2
	CDHR5	ENST00000358353.8	TSL:5	c.*486C>A		3_prime_UTR	Exon 15 of 15	ENSP00000351118.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000373 AC: 1 AN: 26776 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 14600

African (AFR) AF: 0.00 AC: 0 AN: 328

American (AMR) AF: 0.00 AC: 0 AN: 1194

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 572

East Asian (EAS) AF: 0.00 AC: 0 AN: 586

South Asian (SAS) AF: 0.00 AC: 0 AN: 4536

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1422

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1720

European-Non Finnish (NFE) AF: 0.0000673 AC: 1 AN: 14860

Other (OTH) AF: 0.00 AC: 0 AN: 1558

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 489

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.43
DANN	Benign	0.64
PhyloP100		-0.69

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: rs3758650; hg19: chr11-616865;