rs111033227
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_000260.4(MYO7A):c.1554+8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00321 in 1,551,032 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000260.4 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO7A | NM_000260.4 | c.1554+8G>A | splice_region_variant, intron_variant | ENST00000409709.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO7A | ENST00000409709.9 | c.1554+8G>A | splice_region_variant, intron_variant | 1 | NM_000260.4 | ||||
MYO7A | ENST00000409619.6 | c.1521+8G>A | splice_region_variant, intron_variant | 1 | |||||
MYO7A | ENST00000458637.6 | c.1554+8G>A | splice_region_variant, intron_variant | 1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00242 AC: 368AN: 152176Hom.: 2 Cov.: 32
GnomAD3 exomes AF: 0.00255 AC: 396AN: 155382Hom.: 2 AF XY: 0.00266 AC XY: 219AN XY: 82210
GnomAD4 exome AF: 0.00330 AC: 4618AN: 1398738Hom.: 11 Cov.: 31 AF XY: 0.00330 AC XY: 2275AN XY: 689892
GnomAD4 genome ? AF: 0.00242 AC: 368AN: 152294Hom.: 2 Cov.: 32 AF XY: 0.00239 AC XY: 178AN XY: 74452
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:3
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Mar 11, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 12, 2018 | This variant is associated with the following publications: (PMID: 22135276, 16470552) - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2022 | MYO7A: BP4 - |
Autosomal recessive nonsyndromic hearing loss 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Usher syndrome type 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 20, 2015 | c.1554+8G>A in intron 13 of MYO7A: This variant is not expected to have clinical significance because it is not located within the conserved region of the splic e consensus sequence and has been identified in 1.7% (5/298) of Finnish chromoso mes and in 0.4% (33/8958) of European chromosomes by the Exome Aggregation Conso rtium (ExAC, http://exac.broadinstitute.org; dbSNP rs111033227. - |
Autosomal dominant nonsyndromic hearing loss 11 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Usher syndrome type 1B Benign:1
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Apr 16, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at