rs9941051

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004360.5(CDH1):​c.163+23060C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.867 in 152,276 control chromosomes in the GnomAD database, including 57,367 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 0.87 ( 57367 hom., cov: 33)

Consequence

CDH1
NM_004360.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.671
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 -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CDH1NM_004360.5 linkc.163+23060C>T intron_variant Intron 2 of 15 ENST00000261769.10 NP_004351.1 P12830-1A0A0U2ZQU7B3GN61
CDH1NM_001317184.2 linkc.163+23060C>T intron_variant Intron 2 of 14 NP_001304113.1 P12830-2B3GN61
CDH1NM_001317185.2 linkc.-1453+23060C>T intron_variant Intron 2 of 15 NP_001304114.1 P12830B3GN61Q9UII7
CDH1NM_001317186.2 linkc.-1657+23060C>T intron_variant Intron 2 of 14 NP_001304115.1 P12830B3GN61

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CDH1ENST00000261769.10 linkc.163+23060C>T intron_variant Intron 2 of 15 1 NM_004360.5 ENSP00000261769.4 P12830-1
CDH1ENST00000422392.6 linkc.163+23060C>T intron_variant Intron 2 of 14 1 ENSP00000414946.2 P12830-2
CDH1ENST00000566612.5 linkn.163+23060C>T intron_variant Intron 2 of 14 1 ENSP00000454782.1 H3BNC6
CDH1ENST00000566510.5 linkn.163+23060C>T intron_variant Intron 2 of 14 5 ENSP00000458139.1 H3BVI7

Frequencies

GnomAD3 genomes
AF:
0.867
AC:
131905
AN:
152158
Hom.:
57339
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.871
Gnomad AMI
AF:
0.924
Gnomad AMR
AF:
0.824
Gnomad ASJ
AF:
0.929
Gnomad EAS
AF:
0.775
Gnomad SAS
AF:
0.784
Gnomad FIN
AF:
0.825
Gnomad MID
AF:
0.876
Gnomad NFE
AF:
0.889
Gnomad OTH
AF:
0.876
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.867
AC:
131987
AN:
152276
Hom.:
57367
Cov.:
33
AF XY:
0.861
AC XY:
64073
AN XY:
74446
show subpopulations
Gnomad4 AFR
AF:
0.871
Gnomad4 AMR
AF:
0.823
Gnomad4 ASJ
AF:
0.929
Gnomad4 EAS
AF:
0.775
Gnomad4 SAS
AF:
0.784
Gnomad4 FIN
AF:
0.825
Gnomad4 NFE
AF:
0.889
Gnomad4 OTH
AF:
0.872
Alfa
AF:
0.870
Hom.:
11231
Bravo
AF:
0.866
Asia WGS
AF:
0.796
AC:
2771
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
0.47
DANN
Benign
0.79

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: rs9941051; hg19: chr16-68795374; API