rs16958383

Variant names:

• chr16-68823097-G-A
• rs16958383
• NM_004360.5:c.1937-302G>A

Variant summary

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

The NM_004360.5(CDH1):​c.1937-302G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 364,374 control chromosomes in the GnomAD database, including 5,473 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (2980 hom., cov: 30)
  • Exomes 𝑓: 0.14 (2493 hom.)
• Consequence: CDH1 NM_004360.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.68

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]

FTLP14 (HGNC:37964): (ferritin light chain pseudogene 14)

ENSG00000260798 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 16-68823097-G-A is Benign according to our data. Variant chr16-68823097-G-A is described in ClinVar as [Benign]. Clinvar id is 1250701.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH1	NM_004360.5	c.1937-302G>A		intron_variant	Intron 12 of 15	ENST00000261769.10	NP_004351.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH1	ENST00000261769.10	c.1937-302G>A		intron_variant	Intron 12 of 15	1	NM_004360.5	ENSP00000261769.4

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28336 AN: 151728 Hom.: 2972 Cov.: 30

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.0703

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.0811

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.166

GnomAD4 exome AF: 0.144 AC: 30686 AN: 212524 Hom.: 2493 Cov.: 0 AF XY: 0.139 AC XY: 15769 AN XY: 113688

Gnomad4 AFR exome AF: 0.286

Gnomad4 AMR exome AF: 0.120

Gnomad4 ASJ exome AF: 0.142

Gnomad4 EAS exome AF: 0.176

Gnomad4 SAS exome AF: 0.0795

Gnomad4 FIN exome AF: 0.162

Gnomad4 NFE exome AF: 0.149

Gnomad4 OTH exome AF: 0.154

GnomAD4 genome AF: 0.187 AC: 28362 AN: 151850 Hom.: 2980 Cov.: 30 AF XY: 0.182 AC XY: 13531 AN XY: 74242

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.195

Gnomad4 SAS AF: 0.0802

Gnomad4 FIN AF: 0.159

Gnomad4 NFE AF: 0.152

Gnomad4 OTH AF: 0.165

Alfa AF: 0.154 Hom.: 3063

Bravo AF: 0.193

Asia WGS AF: 0.132 AC: 460 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 24, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.2
DANN	Benign	0.58

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: rs16958383; hg19: chr16-68857000;