16-68737475-C-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_004360.5(CDH1):​c.48+12C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 37)

Consequence

CDH1
NM_004360.5 intron

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0130
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
Variant 16-68737475-C-G is Benign according to our data. Variant chr16-68737475-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 918387.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CDH1NM_004360.5 linkuse as main transcriptc.48+12C>G intron_variant ENST00000261769.10 NP_004351.1
CDH1NM_001317184.2 linkuse as main transcriptc.48+12C>G intron_variant NP_001304113.1
CDH1NM_001317185.2 linkuse as main transcriptc.-1568+12C>G intron_variant NP_001304114.1
CDH1NM_001317186.2 linkuse as main transcriptc.-1772+12C>G intron_variant NP_001304115.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CDH1ENST00000261769.10 linkuse as main transcriptc.48+12C>G intron_variant 1 NM_004360.5 ENSP00000261769 P1P12830-1
CDH1ENST00000422392.6 linkuse as main transcriptc.48+12C>G intron_variant 1 ENSP00000414946 P12830-2
CDH1ENST00000566612.5 linkuse as main transcriptc.48+12C>G intron_variant, NMD_transcript_variant 1 ENSP00000454782
CDH1ENST00000566510.5 linkuse as main transcriptc.48+12C>G intron_variant, NMD_transcript_variant 5 ENSP00000458139

Frequencies

GnomAD3 genomes
Cov.:
37
GnomAD4 exome
Cov.:
35
GnomAD4 genome
Cov.:
37
Bravo
AF:
0.00000378

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitterclinical testingColor Diagnostics, LLC DBA Color HealthMar 11, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
CADD
Benign
4.8
DANN
Benign
0.57

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1221801902; hg19: chr16-68771378; API