16-68737332-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004360.5(CDH1):​c.-84G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000707 in 1,174,648 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0033 ( 7 hom., cov: 33)
Exomes 𝑓: 0.00032 ( 6 hom. )

Consequence

CDH1
NM_004360.5 5_prime_UTR

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0350
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 -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.58).
BP6
Variant 16-68737332-G-A is Benign according to our data. Variant chr16-68737332-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 492675.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00333 (508/152342) while in subpopulation AFR AF= 0.0117 (485/41588). AF 95% confidence interval is 0.0108. There are 7 homozygotes in gnomad4. There are 237 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 508 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CDH1NM_004360.5 linkuse as main transcriptc.-84G>A 5_prime_UTR_variant 1/16 ENST00000261769.10 NP_004351.1
CDH1NM_001317184.2 linkuse as main transcriptc.-84G>A 5_prime_UTR_variant 1/15 NP_001304113.1
CDH1NM_001317185.2 linkuse as main transcriptc.-1699G>A 5_prime_UTR_variant 1/16 NP_001304114.1
CDH1NM_001317186.2 linkuse as main transcriptc.-1903G>A 5_prime_UTR_variant 1/15 NP_001304115.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CDH1ENST00000261769.10 linkuse as main transcriptc.-84G>A 5_prime_UTR_variant 1/161 NM_004360.5 ENSP00000261769 P1P12830-1
CDH1ENST00000566612.5 linkuse as main transcriptc.-84G>A 5_prime_UTR_variant, NMD_transcript_variant 1/151 ENSP00000454782
CDH1ENST00000422392.6 linkuse as main transcript upstream_gene_variant 1 ENSP00000414946 P12830-2
CDH1ENST00000566510.5 linkuse as main transcript upstream_gene_variant 5 ENSP00000458139

Frequencies

GnomAD3 genomes
AF:
0.00333
AC:
507
AN:
152228
Hom.:
7
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0117
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000851
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00430
GnomAD4 exome
AF:
0.000316
AC:
323
AN:
1022306
Hom.:
6
Cov.:
13
AF XY:
0.000279
AC XY:
144
AN XY:
516370
show subpopulations
Gnomad4 AFR exome
AF:
0.0124
Gnomad4 AMR exome
AF:
0.000271
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000151
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000208
Gnomad4 OTH exome
AF:
0.000482
GnomAD4 genome
AF:
0.00333
AC:
508
AN:
152342
Hom.:
7
Cov.:
33
AF XY:
0.00318
AC XY:
237
AN XY:
74498
show subpopulations
Gnomad4 AFR
AF:
0.0117
Gnomad4 AMR
AF:
0.000850
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00426
Alfa
AF:
0.00208
Hom.:
0
Bravo
AF:
0.00350
Asia WGS
AF:
0.000866
AC:
3
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, no assertion criteria providedclinical testingMayo Clinic Laboratories, Mayo Clinic-- -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingGeneDxJun 25, 2018- -
Malignant tumor of prostate Benign:1
Likely benign, criteria provided, single submitterclinical testingKCCC/NGS Laboratory, Kuwait Cancer Control CenterJul 07, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.58
CADD
Benign
14
DANN
Benign
0.92

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs374268061; hg19: chr16-68771235; API