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GeneBe

rs9929218

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.560
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 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
CDH1NM_004360.5 linkuse as main transcriptc.164-14627G>A intron_variant ENST00000261769.10
CDH1NM_001317184.2 linkuse as main transcriptc.164-14627G>A intron_variant
CDH1NM_001317185.2 linkuse as main transcriptc.-1452-14627G>A intron_variant
CDH1NM_001317186.2 linkuse as main transcriptc.-1656-14627G>A intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CDH1ENST00000261769.10 linkuse as main transcriptc.164-14627G>A intron_variant 1 NM_004360.5 P1P12830-1

Frequencies

GnomAD3 genomes
AF:
0.284
AC:
43088
AN:
151968
Hom.:
6233
Cov.:
32
show subpopulations
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
show subpopulations
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
LINK: link

Submissions by phenotype

Hereditary diffuse gastric adenocarcinoma Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 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

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

Other links and lift over

dbSNP: rs9929218; hg19: chr16-68820946; API