rs7499886

Positions:

• chr16-66379292-G-A
• chr16-66379292-G-C
• chr16-66379292-G-T

Variant summary

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

The NM_001795.5(CDH5):​c.-19-27G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 1,527,282 control chromosomes in the GnomAD database, including 147,183 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 0.47 (17458 hom., cov: 33)
  • Exomes 𝑓: 0.43 (129725 hom.)
• Consequence: CDH5 NM_001795.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

Genes affected

CDH5 (HGNC:1764): (cadherin 5) This gene encodes a classical cadherin of the cadherin superfamily. The encoded preproprotein is proteolytically processed to generate the mature glycoprotein. This calcium-dependent cell-cell adhesion molecule is comprised of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. Functioning as a classical cadherin by imparting to cells the ability to adhere in a homophilic manner, this protein plays a role in endothelial adherens junction assembly and maintenance. This gene is located in a gene cluster in a region on the long arm of chromosome 16 that is involved in loss of heterozygosity events in breast and prostate cancer. [provided by RefSeq, Nov 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH5	NM_001795.5	c.-19-27G>A		intron_variant		ENST00000341529.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH5	ENST00000341529.8	c.-19-27G>A		intron_variant		1	NM_001795.5	P1

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71773 AN: 151940 Hom.: 17437 Cov.: 33

Gnomad AFR AF: 0.548

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.595

Gnomad ASJ AF: 0.485

Gnomad EAS AF: 0.496

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.502

GnomAD3 exomes AF: 0.469 AC: 107224 AN: 228704 Hom.: 26409 AF XY: 0.458 AC XY: 56547 AN XY: 123342

Gnomad AFR exome AF: 0.548

Gnomad AMR exome AF: 0.686

Gnomad ASJ exome AF: 0.500

Gnomad EAS exome AF: 0.497

Gnomad SAS exome AF: 0.409

Gnomad FIN exome AF: 0.342

Gnomad NFE exome AF: 0.424

Gnomad OTH exome AF: 0.467

GnomAD4 exome AF: 0.430 AC: 591091 AN: 1375222 Hom.: 129725 Cov.: 21 AF XY: 0.430 AC XY: 292115 AN XY: 679974

Gnomad4 AFR exome AF: 0.548

Gnomad4 AMR exome AF: 0.675

Gnomad4 ASJ exome AF: 0.502

Gnomad4 EAS exome AF: 0.508

Gnomad4 SAS exome AF: 0.414

Gnomad4 FIN exome AF: 0.347

Gnomad4 NFE exome AF: 0.417

Gnomad4 OTH exome AF: 0.442

GnomAD4 genome AF: 0.472 AC: 71838 AN: 152060 Hom.: 17458 Cov.: 33 AF XY: 0.468 AC XY: 34814 AN XY: 74320

Gnomad4 AFR AF: 0.548

Gnomad4 AMR AF: 0.596

Gnomad4 ASJ AF: 0.485

Gnomad4 EAS AF: 0.496

Gnomad4 SAS AF: 0.404

Gnomad4 FIN AF: 0.331

Gnomad4 NFE AF: 0.424

Gnomad4 OTH AF: 0.500

Alfa AF: 0.443 Hom.: 33735

Bravo AF: 0.498

Asia WGS AF: 0.432 AC: 1503 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.71
DANN	Benign	0.56

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: rs7499886; hg19: chr16-66413195; COSMIC: COSV58519323;