chr5-141573477-G-C
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_005219.5(DIAPH1):c.2358+15C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000915 in 1,321,998 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.00038 ( 0 hom., cov: 28)
Exomes 𝑓: 0.000055 ( 0 hom. )
Consequence
DIAPH1
NM_005219.5 intron
NM_005219.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.333
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 -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
Variant 5-141573477-G-C is Benign according to our data. Variant chr5-141573477-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 227302.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.0000554 (65/1173456) while in subpopulation AFR AF= 0.00186 (50/26924). AF 95% confidence interval is 0.00145. There are 0 homozygotes in gnomad4_exome. There are 29 alleles in male gnomad4_exome subpopulation. Median coverage is 38. This position pass quality control queck.
BS2
High AC in GnomAd4 at 56 AD gene.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DIAPH1 | ENST00000389054.8 | c.2358+15C>G | intron_variant | Intron 16 of 27 | 5 | NM_005219.5 | ENSP00000373706.4 | |||
DIAPH1 | ENST00000518047.5 | c.2331+15C>G | intron_variant | Intron 15 of 26 | 5 | ENSP00000428268.2 | ||||
DIAPH1 | ENST00000647433.1 | c.2358+15C>G | intron_variant | Intron 16 of 28 | ENSP00000494675.1 |
Frequencies
GnomAD3 genomes AF: 0.000377 AC: 56AN: 148454Hom.: 0 Cov.: 28
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GnomAD3 exomes AF: 0.0000742 AC: 18AN: 242530Hom.: 0 AF XY: 0.0000453 AC XY: 6AN XY: 132510
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GnomAD4 exome AF: 0.0000554 AC: 65AN: 1173456Hom.: 0 Cov.: 38 AF XY: 0.0000489 AC XY: 29AN XY: 593456
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GnomAD4 genome AF: 0.000377 AC: 56AN: 148542Hom.: 0 Cov.: 28 AF XY: 0.000276 AC XY: 20AN XY: 72460
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 30, 2012 | 2358+15C>G in Intron 16 of DIAPH1: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus se quence and has been identified in 0.1% (4/2940) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.was hington.edu/EVS). - |
Autosomal dominant nonsyndromic hearing loss 1;C5567650:Progressive microcephaly-seizures-cortical blindness-developmental delay syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 07, 2025 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at