chr16-68829411-T-C

Position:

• chr16-68829411-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000261769.10(CDH1):​c.2296-243T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0858 in 152,248 control chromosomes in the GnomAD database, including 572 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.086 (572 hom., cov: 32)
• Consequence: CDH1 ENST00000261769.10 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.192

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 16-68829411-T-C is Benign according to our data. Variant chr16-68829411-T-C is described in ClinVar as [Benign]. Clinvar id is 1260987.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH1	NM_004360.5	c.2296-243T>C		intron_variant		ENST00000261769.10	NP_004351.1
CDH1	NM_001317184.2	c.2113-243T>C		intron_variant			NP_001304113.1
CDH1	NM_001317185.2	c.748-243T>C		intron_variant			NP_001304114.1
CDH1	NM_001317186.2	c.331-243T>C		intron_variant			NP_001304115.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH1	ENST00000261769.10	c.2296-243T>C		intron_variant		1	NM_004360.5	ENSP00000261769	P1

Frequencies

GnomAD3 genomes AF: 0.0857 AC: 13032 AN: 152130 Hom.: 565 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0990

Gnomad ASJ AF: 0.0680

Gnomad EAS AF: 0.0747

Gnomad SAS AF: 0.0602

Gnomad FIN AF: 0.0683

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.0744

Gnomad OTH AF: 0.0737

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

GnomAD4 genome AF: 0.0858 AC: 13064 AN: 152248 Hom.: 572 Cov.: 32 AF XY: 0.0852 AC XY: 6345 AN XY: 74452

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.0990

Gnomad4 ASJ AF: 0.0680

Gnomad4 EAS AF: 0.0739

Gnomad4 SAS AF: 0.0607

Gnomad4 FIN AF: 0.0683

Gnomad4 NFE AF: 0.0744

Gnomad4 OTH AF: 0.0800

Alfa AF: 0.0771 Hom.: 367

Bravo AF: 0.0917

Asia WGS AF: 0.0970 AC: 336 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 07, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.8
DANN	Benign	0.76

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: rs2276329; hg19: chr16-68863314;