rs876657462
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate
The NM_031475.3(ESPN):c.2405+12G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,614,076 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 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
ESPN
NM_031475.3 intron
NM_031475.3 intron
Scores
5
Clinical Significance
Conservation
PhyloP100: -0.507
Genes affected
ESPN (HGNC:13281): (espin) This gene encodes a multifunctional actin-bundling protein. It plays a major role in regulating the organization, dimensions, dynamics, and signaling capacities of the actin filament-rich, microvillus-type specializations that mediate sensory transduction in various mechanosensory and chemosensory cells. Mutations in this gene are associated with autosomal recessive neurosensory deafness, and autosomal dominant sensorineural deafness without vestibular involvement. [provided by RefSeq, Nov 2009]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_addAF=-0.299049).
BP6
Variant 1-6457275-G-A is Benign according to our data. Variant chr1-6457275-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 227361.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ESPN | NM_031475.3 | c.2405+12G>A | intron_variant | ENST00000645284.1 | |||
ESPN | NM_001367473.1 | c.2315+12G>A | intron_variant | ||||
ESPN | NM_001367474.1 | c.2342+12G>A | intron_variant | ||||
ESPN | XM_017002433.2 | c.2342+12G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ESPN | ENST00000645284.1 | c.2405+12G>A | intron_variant | NM_031475.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152242Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251186Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135800
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GnomAD4 exome AF: 0.0000144 AC: 21AN: 1461834Hom.: 0 Cov.: 33 AF XY: 0.0000110 AC XY: 8AN XY: 727208
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152242Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74376
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
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 | Mar 29, 2016 | c.2405+12G>A in intron 11 of ESPN: This variant is not expected to have clinical significance because it is not located within the splice consensus sequence. - |
Computational scores
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BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
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Benign
DANN
Benign
FATHMM_MKL
Benign
N
MutationTaster
Benign
N;N;N
GERP RS
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at