rs1078621

Positions:

• chr16-68745093-G-A

Variant summary

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

The NM_004360.5(CDH1):​c.163+6682G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 151,620 control chromosomes in the GnomAD database, including 19,078 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 0.48 (19078 hom., cov: 29)
• Consequence: CDH1 NM_004360.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0300

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=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH1	NM_004360.5	c.163+6682G>A		intron_variant		ENST00000261769.10
CDH1	NM_001317184.2	c.163+6682G>A		intron_variant
CDH1	NM_001317185.2	c.-1453+6682G>A		intron_variant
CDH1	NM_001317186.2	c.-1657+6682G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH1	ENST00000261769.10	c.163+6682G>A		intron_variant		1	NM_004360.5	P1
CDH1	ENST00000422392.6	c.163+6682G>A		intron_variant		1
CDH1	ENST00000566612.5	c.163+6682G>A		intron_variant, NMD_transcript_variant		1
CDH1	ENST00000566510.5	c.163+6682G>A		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73453 AN: 151502 Hom.: 19080 Cov.: 29

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.519

Gnomad EAS AF: 0.491

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.507

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

GnomAD4 genome AF: 0.485 AC: 73470 AN: 151620 Hom.: 19078 Cov.: 29 AF XY: 0.484 AC XY: 35840 AN XY: 74034

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.474

Gnomad4 ASJ AF: 0.519

Gnomad4 EAS AF: 0.490

Gnomad4 SAS AF: 0.537

Gnomad4 FIN AF: 0.578

Gnomad4 NFE AF: 0.585

Gnomad4 OTH AF: 0.508

Alfa AF: 0.538 Hom.: 10415

Bravo AF: 0.467

Asia WGS AF: 0.471 AC: 1640 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	2.2
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: rs1078621; hg19: chr16-68778996; COSMIC: COSV55741854; COSMIC: COSV55741854;