rs4612730
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_001001974.4(PLEKHA1):c.612+934G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 153,858 control chromosomes in the GnomAD database, including 18,122 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.48 ( 17813 hom., cov: 29)
Exomes 𝑓: 0.49 ( 309 hom. )
Consequence
PLEKHA1
NM_001001974.4 intron
NM_001001974.4 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.428
Genes affected
PLEKHA1 (HGNC:14335): (pleckstrin homology domain containing A1) This gene encodes a pleckstrin homology domain-containing adapter protein. The encoded protein is localized to the plasma membrane where it specifically binds phosphatidylinositol 3,4-bisphosphate. This protein may be involved in the formation of signaling complexes in the plasma membrane. Polymorphisms in this gene are associated with age-related macular degeneration. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 5.[provided by RefSeq, Sep 2010]
MIR3941 (HGNC:38949): (microRNA 3941) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLEKHA1 | NM_001001974.4 | c.612+934G>A | intron_variant | ENST00000368990.8 | |||
MIR3941 | NR_037506.1 | upstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLEKHA1 | ENST00000368990.8 | c.612+934G>A | intron_variant | 1 | NM_001001974.4 | P3 | |||
MIR3941 | ENST00000582572.1 | upstream_gene_variant |
Frequencies
GnomAD3 genomes ? AF: 0.476 AC: 72057AN: 151252Hom.: 17791 Cov.: 29
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GnomAD3 exomes AF: 0.470 AC: 2704AN: 5750Hom.: 630 AF XY: 0.467 AC XY: 1263AN XY: 2704
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GnomAD4 exome AF: 0.489 AC: 1217AN: 2488Hom.: 309 Cov.: 0 AF XY: 0.500 AC XY: 641AN XY: 1282
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GnomAD4 genome ? AF: 0.476 AC: 72118AN: 151370Hom.: 17813 Cov.: 29 AF XY: 0.488 AC XY: 36093AN XY: 73914
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ClinVar
Not reported inComputational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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