rs35741240
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2
The NM_004360.5(CDH1):c.1680G>A(p.Thr560Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000093 in 1,613,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. T560T) has been classified as Likely benign.
Frequency
Consequence
NM_004360.5 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
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CDH1 | NM_004360.5 | c.1680G>A | p.Thr560Thr | synonymous_variant | Exon 11 of 16 | ENST00000261769.10 | NP_004351.1 | |
CDH1 | NM_001317184.2 | c.1497G>A | p.Thr499Thr | synonymous_variant | Exon 10 of 15 | NP_001304113.1 | ||
CDH1 | NM_001317185.2 | c.132G>A | p.Thr44Thr | synonymous_variant | Exon 11 of 16 | NP_001304114.1 | ||
CDH1 | NM_001317186.2 | c.-254-2607G>A | intron_variant | Intron 10 of 14 | NP_001304115.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152116Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251482Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135914
GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461514Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6AN XY: 727044
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152116Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74294
ClinVar
Submissions by phenotype
Hereditary diffuse gastric adenocarcinoma Uncertain:1Benign:3
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PM2 (PMID: 30311375) -
This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing. -
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Hereditary cancer-predisposing syndrome Benign:2
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This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
not specified Benign:1
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not provided Benign:1
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Malignant tumor of prostate Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at