16-68737372-G-A
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBS2_Supporting
The NM_004360.5(CDH1):c.-44G>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 0.0000158 in 1,517,956 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 -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CDH1 | NM_004360.5 | c.-44G>A | 5_prime_UTR_variant | Exon 1 of 16 | ENST00000261769.10 | NP_004351.1 | ||
CDH1 | NM_001317184.2 | c.-44G>A | 5_prime_UTR_variant | Exon 1 of 15 | NP_001304113.1 | |||
CDH1 | NM_001317185.2 | c.-1659G>A | 5_prime_UTR_variant | Exon 1 of 16 | NP_001304114.1 | |||
CDH1 | NM_001317186.2 | c.-1863G>A | 5_prime_UTR_variant | Exon 1 of 15 | NP_001304115.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152210Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000164 AC: 2AN: 122118Hom.: 0 AF XY: 0.0000149 AC XY: 1AN XY: 67166
GnomAD4 exome AF: 0.0000132 AC: 18AN: 1365630Hom.: 0 Cov.: 28 AF XY: 0.0000148 AC XY: 10AN XY: 674132
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152326Hom.: 0 Cov.: 33 AF XY: 0.0000268 AC XY: 2AN XY: 74494
ClinVar
Submissions by phenotype
not provided Uncertain:1
This variant is denoted CDH1 c.-44G>A, and describes a nucleotide substitution 44 base pairs upstream of the CDH1 ATG translational start site in the 5' untranslated region (UTR). The surrounding sequence, with the base that is substituted in braces, is ACCC[G/A]ACCG. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. This variant does not appear to affect the start codon or the Kozak translational consensus sequence. CDH1 c.-44G>A was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations, and the base that is altered, a guanine (G) is not conserved. Based on currently available information, it is unclear whether CDH1 c.-44G>A is pathogenic or benign. We consider it to be a variant of uncertain significance. -
Hereditary diffuse gastric adenocarcinoma Uncertain:1
Not applicable criteria (PMID: 30311375) -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at