rs8061932

chr16-68828694-T-C

Variant summary

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

The NM_004360.5(CDH1):c.2295+390T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 152,110 control chromosomes in the GnomAD database, including 7,403 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 0.27 (7403 hom., cov: 32)
• Consequence: CDH1 NM_004360.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.318

Genes affected

CDH1 (HGNC:1748): (cadherin 1) This gene encodes a classical cadherin of the cadherin superfamily. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature glycoprotein. This calcium-dependent cell-cell adhesion protein is comprised of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. Mutations in this gene are correlated with gastric, breast, colorectal, thyroid and ovarian cancer. Loss of function of this gene is thought to contribute to cancer progression by increasing proliferation, invasion, and/or metastasis. The ectodomain of this protein mediates bacterial adhesion to mammalian cells and the cytoplasmic domain is required for internalization. This gene is present in a gene cluster with other members of the cadherin family on chromosome 16. [provided by RefSeq, Nov 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH1	NM_004360.5	c.2295+390T>C		intron_variant		ENST00000261769.10
CDH1	NM_001317184.2	c.2112+390T>C		intron_variant
CDH1	NM_001317185.2	c.747+390T>C		intron_variant
CDH1	NM_001317186.2	c.330+390T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH1	ENST00000261769.10	c.2295+390T>C		intron_variant		1	NM_004360.5	P1

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40678 AN: 151994 Hom.: 7380 Cov.: 32

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.271

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.268 AC: 40742 AN: 152110 Hom.: 7403 Cov.: 32 AF XY: 0.262 AC XY: 19513 AN XY: 74378

Gnomad4 AFR AF: 0.530

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.209

Gnomad4 SAS AF: 0.0993

Gnomad4 FIN AF: 0.171

Gnomad4 NFE AF: 0.166

Gnomad4 OTH AF: 0.228

Alfa AF: 0.179 Hom.: 1976

Bravo AF: 0.285

Asia WGS AF: 0.159 AC: 552 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	6.2
Dann	Benign	0.75

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: rs8061932; hg19: chr16-68862597;