rs34269395
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The NM_006017.3(PROM1):c.2374-4_2374-3insC variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 1,485,620 control chromosomes in the GnomAD database, including 51,835 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.29 ( 6655 hom., cov: 0)
Exomes 𝑓: 0.26 ( 45180 hom. )
Consequence
PROM1
NM_006017.3 splice_region, splice_polypyrimidine_tract, intron
NM_006017.3 splice_region, splice_polypyrimidine_tract, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.539
Genes affected
PROM1 (HGNC:9454): (prominin 1) This gene encodes a pentaspan transmembrane glycoprotein. The protein localizes to membrane protrusions and is often expressed on adult stem cells, where it is thought to function in maintaining stem cell properties by suppressing differentiation. Mutations in this gene have been shown to result in retinitis pigmentosa and Stargardt disease. Expression of this gene is also associated with several types of cancer. This gene is expressed from at least five alternative promoters that are expressed in a tissue-dependent manner. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP6
?
Variant 4-15980540-A-AG is Benign according to our data. Variant chr4-15980540-A-AG is described in ClinVar as [Likely_benign]. Clinvar id is 95333.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PROM1 | NM_006017.3 | c.2374-4_2374-3insC | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000447510.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PROM1 | ENST00000447510.7 | c.2374-4_2374-3insC | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_006017.3 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.292 AC: 44022AN: 150920Hom.: 6657 Cov.: 0
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GnomAD3 exomes AF: 0.282 AC: 41237AN: 146440Hom.: 5795 AF XY: 0.278 AC XY: 21518AN XY: 77404
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GnomAD4 exome AF: 0.256 AC: 341110AN: 1334584Hom.: 45180 Cov.: 26 AF XY: 0.256 AC XY: 169101AN XY: 660612
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GnomAD4 genome ? AF: 0.292 AC: 44029AN: 151036Hom.: 6655 Cov.: 0 AF XY: 0.294 AC XY: 21696AN XY: 73748
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Eurofins Ntd Llc (ga) | Aug 14, 2013 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 07, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Retinitis Pigmentosa, Recessive Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Stargardt Disease, Dominant Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Macular dystrophy, retinal Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Cone-Rod Dystrophy, Dominant Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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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