rs9925161

chr16-68828001-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004360.5(CDH1):c.2165-173G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0561 in 152,252 control chromosomes in the GnomAD database, including 306 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.056 (306 hom., cov: 32)
• Consequence: CDH1 NM_004360.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.268

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 16-68828001-G-A is Benign according to our data. Variant chr16-68828001-G-A is described in ClinVar as [Benign]. Clinvar id is 1231648.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0919 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH1	NM_004360.5	c.2165-173G>A		intron_variant		ENST00000261769.10
CDH1	NM_001317184.2	c.1982-173G>A		intron_variant
CDH1	NM_001317185.2	c.617-173G>A		intron_variant
CDH1	NM_001317186.2	c.200-173G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH1	ENST00000261769.10	c.2165-173G>A		intron_variant		1	NM_004360.5	P1

Frequencies

GnomAD3 genomes AF: 0.0560 AC: 8512 AN: 152134 Hom.: 303 Cov.: 32

Gnomad AFR AF: 0.0942

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0795

Gnomad ASJ AF: 0.0199

Gnomad EAS AF: 0.0721

Gnomad SAS AF: 0.0581

Gnomad FIN AF: 0.0213

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0343

Gnomad OTH AF: 0.0473

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

GnomAD4 genome AF: 0.0561 AC: 8540 AN: 152252 Hom.: 306 Cov.: 32 AF XY: 0.0564 AC XY: 4195 AN XY: 74444

Gnomad4 AFR AF: 0.0944

Gnomad4 AMR AF: 0.0795

Gnomad4 ASJ AF: 0.0199

Gnomad4 EAS AF: 0.0713

Gnomad4 SAS AF: 0.0579

Gnomad4 FIN AF: 0.0213

Gnomad4 NFE AF: 0.0343

Gnomad4 OTH AF: 0.0535

Alfa AF: 0.0401 Hom.: 65

Bravo AF: 0.0627

Asia WGS AF: 0.0910 AC: 314 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 25, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	4.5
Dann	Benign	0.60

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: rs9925161; hg19: chr16-68861904; COSMIC: COSV55731728; COSMIC: COSV55731728;