rs150567427
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PVS1_ModerateBS1BS2
The NM_153676.4(USH1C):c.2014-1G>A variant causes a splice acceptor, intron change. The variant allele was found at a frequency of 0.000323 in 1,614,178 control chromosomes in the GnomAD database, including 6 homozygotes. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_153676.4 splice_acceptor, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
USH1C | NM_153676.4 | c.2014-1G>A | splice_acceptor_variant, intron_variant | Intron 18 of 26 | ENST00000005226.12 | NP_710142.1 | ||
USH1C | NM_005709.4 | c.1285-3970G>A | intron_variant | Intron 15 of 20 | ENST00000318024.9 | NP_005700.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
USH1C | ENST00000005226.12 | c.2014-1G>A | splice_acceptor_variant, intron_variant | Intron 18 of 26 | 5 | NM_153676.4 | ENSP00000005226.7 | |||
USH1C | ENST00000318024.9 | c.1285-3970G>A | intron_variant | Intron 15 of 20 | 1 | NM_005709.4 | ENSP00000317018.4 |
Frequencies
GnomAD3 genomes AF: 0.00171 AC: 261AN: 152200Hom.: 2 Cov.: 33
GnomAD3 exomes AF: 0.000418 AC: 105AN: 251310Hom.: 1 AF XY: 0.000346 AC XY: 47AN XY: 135872
GnomAD4 exome AF: 0.000178 AC: 260AN: 1461860Hom.: 4 Cov.: 31 AF XY: 0.000160 AC XY: 116AN XY: 727228
GnomAD4 genome AF: 0.00172 AC: 262AN: 152318Hom.: 2 Cov.: 33 AF XY: 0.00170 AC XY: 127AN XY: 74492
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
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Has not been previously reported as pathogenic or benign to our knowledge -
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Usher syndrome type 1 Pathogenic:1
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not specified Uncertain:1
The 2014-1G>A variant in USH1C has not been previously reported in individuals w ith hearing loss. It was identified in 0.5% (22/4400) of African American chromo somes by the NHLBI Exome Sequencing Project and in 1.6% (2/122) of African Ameri can chromosomes by the 1000 Genomes Project (http://evs.gs.washington.edu/EVS/; dbSNP rs150567427). Although this variant has been seen in the general populati on, its frequency is not high enough to rule out a pathogenic role. This variant occurs in the invariant region (-1/2) of the 3? splice consensus sequence and c omputational tools suggest an impact to splicing. In summary, while this variant may impact splicing, its frequency in the general population suggests a benign role; therefore, additional information is needed to determine the clinical sign ificance of the 2014-1G>A variant. -
USH1C-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Usher syndrome type 1C Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at