rs879449703
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_004360.5(CDH1):c.-8G>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 0.0000029 in 1,378,874 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 Uncertain significance (★★).
Frequency
Consequence
NM_004360.5 5_prime_UTR
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CDH1 | NM_004360.5 | c.-8G>A | 5_prime_UTR_variant | Exon 1 of 16 | ENST00000261769.10 | NP_004351.1 | ||
CDH1 | NM_001317184.2 | c.-8G>A | 5_prime_UTR_variant | Exon 1 of 15 | NP_001304113.1 | |||
CDH1 | NM_001317185.2 | c.-1623G>A | 5_prime_UTR_variant | Exon 1 of 16 | NP_001304114.1 | |||
CDH1 | NM_001317186.2 | c.-1827G>A | 5_prime_UTR_variant | Exon 1 of 15 | NP_001304115.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000790 AC: 1AN: 126528Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 69612
GnomAD4 exome AF: 0.00000290 AC: 4AN: 1378874Hom.: 0 Cov.: 30 AF XY: 0.00000294 AC XY: 2AN XY: 680406
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not specified Uncertain:2
Variant summary: The CDH1 c.-8G>A variant involves the alteration of a non-conserved 5' UTR nucleotide. One in silico tool predicts a benign outcome for this variant. This variant was found in 1/121892 control chromosomes (gnomAD) at a frequency of 0.0000082, which does not exceed the estimated maximal expected allele frequency of a pathogenic CDH1 variant (0.0000283). The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a "Variant of Uncertain Significance (VUS)," until additional information becomes available. -
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Hereditary cancer-predisposing syndrome Uncertain:1
This variant is located in the 5' untranslated region of the CDH1 gene. Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/126528 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at