rs77312180
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_004360.5(CDH1):c.48+5C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_004360.5 splice_region, intron
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.48+5C>A | splice_region_variant, intron_variant | Intron 1 of 15 | ENST00000261769.10 | NP_004351.1 | ||
CDH1 | NM_001317184.2 | c.48+5C>A | splice_region_variant, intron_variant | Intron 1 of 14 | NP_001304113.1 | |||
CDH1 | NM_001317185.2 | c.-1568+5C>A | splice_region_variant, intron_variant | Intron 1 of 15 | NP_001304114.1 | |||
CDH1 | NM_001317186.2 | c.-1772+5C>A | splice_region_variant, intron_variant | Intron 1 of 14 | NP_001304115.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CDH1 | ENST00000261769.10 | c.48+5C>A | splice_region_variant, intron_variant | Intron 1 of 15 | 1 | NM_004360.5 | ENSP00000261769.4 | |||
CDH1 | ENST00000422392.6 | c.48+5C>A | splice_region_variant, intron_variant | Intron 1 of 14 | 1 | ENSP00000414946.2 | ||||
CDH1 | ENST00000566612.5 | n.48+5C>A | splice_region_variant, intron_variant | Intron 1 of 14 | 1 | ENSP00000454782.1 | ||||
CDH1 | ENST00000566510.5 | n.48+5C>A | splice_region_variant, intron_variant | Intron 1 of 14 | 5 | ENSP00000458139.1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1385312Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 684236
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
The c.48+5C>A intronic variant results from a C to A substitution 5 nucleotides after coding exon 1 in the CDH1 gene. This nucleotide position is poorly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is not predicted to have any significant effect on this splice donor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at