chr16-66379292-G-A

Variant names:

• chr16-66379292-G-A
• rs7499886
• NM_001795.5:c.-19-27G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 19 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001795.5. 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
	CDH5	NM_001795.5	MANE Select	c.-19-27G>A		intron	N/A	NP_001786.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH5	ENST00000341529.8	TSL:1 MANE Select	c.-19-27G>A		intron	N/A	ENSP00000344115.3
	CDH5	ENST00000563425.2	TSL:5	c.-46G>A		5_prime_UTR	Exon 1 of 6	ENSP00000458878.1
	CDH5	ENST00000649567.1		c.-19-27G>A		intron	N/A	ENSP00000497290.1

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

GnomAD2 exomes AF: 0.469 AC: 107224 AN: 228704 AF XY: 0.458

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 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

African (AFR) AF: 0.548 AC: 17269 AN: 31528

American (AMR) AF: 0.675 AC: 27514 AN: 40740

Ashkenazi Jewish (ASJ) AF: 0.502 AC: 12002 AN: 23906

East Asian (EAS) AF: 0.508 AC: 19688 AN: 38732

South Asian (SAS) AF: 0.414 AC: 33059 AN: 79764

European-Finnish (FIN) AF: 0.347 AC: 18168 AN: 52346

Middle Eastern (MID) AF: 0.480 AC: 1889 AN: 3936

European-Non Finnish (NFE) AF: 0.417 AC: 436300 AN: 1047314

Other (OTH) AF: 0.442 AC: 25202 AN: 56956

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

African (AFR) AF: 0.548 AC: 22705 AN: 41448

American (AMR) AF: 0.596 AC: 9104 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.485 AC: 1683 AN: 3472

East Asian (EAS) AF: 0.496 AC: 2557 AN: 5152

South Asian (SAS) AF: 0.404 AC: 1945 AN: 4820

European-Finnish (FIN) AF: 0.331 AC: 3508 AN: 10584

Middle Eastern (MID) AF: 0.455 AC: 133 AN: 292

European-Non Finnish (NFE) AF: 0.424 AC: 28811 AN: 67976

Other (OTH) AF: 0.500 AC: 1057 AN: 2116

Alfa AF: 0.446 Hom.: 65962

Bravo AF: 0.498

Asia WGS AF: 0.432 AC: 1503 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.71
DANN	Benign	0.56
PhyloP100		-1.2
PromoterAI		0.0038	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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