16-66396564-T-C

Position:

• chr16-66396564-T-C

Variant summary

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

The NM_001795.5(CDH5):​c.1360+363T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 152,102 control chromosomes in the GnomAD database, including 35,993 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 0.69 (35993 hom., cov: 32)
• Consequence: CDH5 NM_001795.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.788 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH5	NM_001795.5	c.1360+363T>C		intron_variant		ENST00000341529.8	NP_001786.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH5	ENST00000341529.8	c.1360+363T>C		intron_variant		1	NM_001795.5	ENSP00000344115.3
CDH5	ENST00000649567.1	c.1360+363T>C		intron_variant				ENSP00000497290.1
CDH5	ENST00000539168.1	c.-324+363T>C		intron_variant		2		ENSP00000461880.1
CDH5	ENST00000565334.5	n.*483+363T>C		intron_variant		5		ENSP00000456028.1

Frequencies

GnomAD3 genomes AF: 0.686 AC: 104208 AN: 151984 Hom.: 35963 Cov.: 32

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.655

Gnomad AMR AF: 0.780

Gnomad ASJ AF: 0.700

Gnomad EAS AF: 0.807

Gnomad SAS AF: 0.690

Gnomad FIN AF: 0.666

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.690

Gnomad OTH AF: 0.711

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

GnomAD4 genome AF: 0.686 AC: 104291 AN: 152102 Hom.: 35993 Cov.: 32 AF XY: 0.687 AC XY: 51058 AN XY: 74332

Gnomad4 AFR AF: 0.632

Gnomad4 AMR AF: 0.780

Gnomad4 ASJ AF: 0.700

Gnomad4 EAS AF: 0.808

Gnomad4 SAS AF: 0.689

Gnomad4 FIN AF: 0.666

Gnomad4 NFE AF: 0.690

Gnomad4 OTH AF: 0.710

Alfa AF: 0.683 Hom.: 8831

Bravo AF: 0.693

Asia WGS AF: 0.710 AC: 2468 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.033
DANN	Benign	0.37

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: rs1073584; hg19: chr16-66430467;