11-616865-G-A

Position:

• chr11-616865-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021924.5(CDHR5):​c.*486C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0494 in 179,030 control chromosomes in the GnomAD database, including 321 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 0.048 (256 hom., cov: 33)
  • Exomes 𝑓: 0.057 (65 hom.)
• Consequence: CDHR5 NM_021924.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.693

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDHR5	NM_021924.5	c.*486C>T		3_prime_UTR_variant	15/15	ENST00000397542.7	NP_068743.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDHR5	ENST00000397542	c.*486C>T		3_prime_UTR_variant	15/15	1	NM_021924.5	ENSP00000380676.2
CDHR5	ENST00000358353	c.*486C>T		3_prime_UTR_variant	15/15	5		ENSP00000351118.4

Frequencies

GnomAD3 genomes AF: 0.0482 AC: 7331 AN: 152166 Hom.: 258 Cov.: 33

Gnomad AFR AF: 0.0171

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.0271

Gnomad ASJ AF: 0.0423

Gnomad EAS AF: 0.0921

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.0929

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0572

Gnomad OTH AF: 0.0396

GnomAD3 exomes AF: 0.0576 AC: 765 AN: 13282 Hom.: 22 AF XY: 0.0576 AC XY: 377 AN XY: 6540

Gnomad AFR exome AF: 0.00718

Gnomad AMR exome AF: 0.0217

Gnomad ASJ exome AF: 0.0542

Gnomad EAS exome AF: 0.0824

Gnomad SAS exome AF: 0.0620

Gnomad FIN exome AF: 0.0946

Gnomad NFE exome AF: 0.0548

Gnomad OTH exome AF: 0.0430

GnomAD4 exome AF: 0.0569 AC: 1522 AN: 26746 Hom.: 65 Cov.: 0 AF XY: 0.0607 AC XY: 885 AN XY: 14574

Gnomad4 AFR exome AF: 0.0213

Gnomad4 AMR exome AF: 0.0151

Gnomad4 ASJ exome AF: 0.0402

Gnomad4 EAS exome AF: 0.0717

Gnomad4 SAS exome AF: 0.0883

Gnomad4 FIN exome AF: 0.0811

Gnomad4 NFE exome AF: 0.0514

Gnomad4 OTH exome AF: 0.0533

GnomAD4 genome AF: 0.0481 AC: 7328 AN: 152284 Hom.: 256 Cov.: 33 AF XY: 0.0512 AC XY: 3814 AN XY: 74452

Gnomad4 AFR AF: 0.0171

Gnomad4 AMR AF: 0.0269

Gnomad4 ASJ AF: 0.0423

Gnomad4 EAS AF: 0.0923

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.0929

Gnomad4 NFE AF: 0.0572

Gnomad4 OTH AF: 0.0388

Alfa AF: 0.0518 Hom.: 343

Bravo AF: 0.0404

Asia WGS AF: 0.0800 AC: 279 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.59
DANN	Benign	0.77

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

Publications

LitVar

Other links and lift over

dbSNP: rs3758650; hg19: chr11-616865; COSMIC: COSV52759201; COSMIC: COSV52759201;