rs9929218

chr16-68787043-G-Achr16-68787043-G-C

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.164-14627G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,086 control chromosomes in the GnomAD database, including 6,233 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.28 (6233 hom., cov: 32)
• Consequence: CDH1 NM_004360.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.560

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=-0.86).
• BP6: Variant 16-68787043-G-A is Benign according to our data. Variant chr16-68787043-G-A is described in ClinVar as [Benign]. Clinvar id is 1623458.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-68787043-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH1	NM_004360.5	c.164-14627G>A		intron_variant		ENST00000261769.10
CDH1	NM_001317184.2	c.164-14627G>A		intron_variant
CDH1	NM_001317185.2	c.-1452-14627G>A		intron_variant
CDH1	NM_001317186.2	c.-1656-14627G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH1	ENST00000261769.10	c.164-14627G>A		intron_variant		1	NM_004360.5	P1

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43088 AN: 151968 Hom.: 6233 Cov.: 32

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.295

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

GnomAD4 genome AF: 0.283 AC: 43112 AN: 152086 Hom.: 6233 Cov.: 32 AF XY: 0.282 AC XY: 20940 AN XY: 74350

Gnomad4 AFR AF: 0.296

Gnomad4 AMR AF: 0.253

Gnomad4 ASJ AF: 0.396

Gnomad4 EAS AF: 0.208

Gnomad4 SAS AF: 0.257

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.290

Gnomad4 OTH AF: 0.293

Alfa AF: 0.281 Hom.: 4776

Bravo AF: 0.281

Asia WGS AF: 0.282 AC: 982 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hereditary diffuse gastric adenocarcinoma Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.48
DANN	Benign	0.62

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: rs9929218; hg19: chr16-68820946;