17-76470891-T-G
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The ENST00000590168.5(RHBDF2):n.2665A>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0143 in 152,258 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.014 ( 51 hom., cov: 34)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
RHBDF2
ENST00000590168.5 non_coding_transcript_exon
ENST00000590168.5 non_coding_transcript_exon
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.125
Genes affected
RHBDF2 (HGNC:20788): (rhomboid 5 homolog 2) Predicted to enable protein transporter activity. Predicted to be involved in negative regulation of protein secretion and regulation of epidermal growth factor receptor signaling pathway. Located in plasma membrane. Implicated in palmoplantar keratoderma-esophageal carcinoma syndrome. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 17-76470891-T-G is Benign according to our data. Variant chr17-76470891-T-G is described in ClinVar as [Benign]. Clinvar id is 369229.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0143 (2170/152258) while in subpopulation AFR AF= 0.0489 (2030/41526). AF 95% confidence interval is 0.0471. There are 51 homozygotes in gnomad4. There are 1027 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
BS2
High AC in GnomAd4 at 2170 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RHBDF2 | NM_001005498.4 | downstream_gene_variant | ENST00000675367.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RHBDF2 | ENST00000590168.5 | n.2665A>C | non_coding_transcript_exon_variant | 12/12 | 1 | ||||
RHBDF2 | ENST00000675367.1 | downstream_gene_variant | NM_001005498.4 | P1 | |||||
RHBDF2 | ENST00000313080.8 | downstream_gene_variant | 1 |
Frequencies
GnomAD3 genomes AF: 0.0143 AC: 2171AN: 152140Hom.: 51 Cov.: 34
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GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 30Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 26
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GnomAD4 genome AF: 0.0143 AC: 2170AN: 152258Hom.: 51 Cov.: 34 AF XY: 0.0138 AC XY: 1027AN XY: 74448
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Palmoplantar keratoderma-esophageal carcinoma syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at