5-141515084-C-CAG
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2
The NM_005219.5(DIAPH1):c.*1765_*1766dupCT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00378 in 152,280 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0038 ( 5 hom., cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
DIAPH1
NM_005219.5 3_prime_UTR
NM_005219.5 3_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.693
Genes affected
DIAPH1 (HGNC:2876): (diaphanous related formin 1) This gene is a homolog of the Drosophila diaphanous gene, and has been linked to autosomal dominant, fully penetrant, nonsyndromic sensorineural progressive low-frequency hearing loss. Actin polymerization involves proteins known to interact with diaphanous protein in Drosophila and mouse. It has therefore been speculated that this gene may have a role in the regulation of actin polymerization in hair cells of the inner ear. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP6
Variant 5-141515084-C-CAG is Benign according to our data. Variant chr5-141515084-C-CAG is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 351253.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1}.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00378 (576/152280) while in subpopulation AMR AF= 0.011 (168/15298). AF 95% confidence interval is 0.00963. There are 5 homozygotes in gnomad4. There are 278 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 576 AD gene.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DIAPH1 | ENST00000389054 | c.*1765_*1766dupCT | 3_prime_UTR_variant | Exon 28 of 28 | 5 | NM_005219.5 | ENSP00000373706.4 | |||
DIAPH1 | ENST00000647433 | c.*1884_*1885dupCT | 3_prime_UTR_variant | Exon 29 of 29 | ENSP00000494675.1 |
Frequencies
GnomAD3 genomes AF: 0.00379 AC: 576AN: 152162Hom.: 5 Cov.: 33
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GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 442Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 264
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GnomAD4 genome AF: 0.00378 AC: 576AN: 152280Hom.: 5 Cov.: 33 AF XY: 0.00373 AC XY: 278AN XY: 74466
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Nonsyndromic Hearing Loss, Mixed Uncertain:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
not provided Benign:1
Feb 01, 2023
CeGaT Center for Human Genetics Tuebingen
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
DIAPH1: BS1, BS2 -
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at