17-74748927-C-T
Variant names:
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP7BS2
The NM_004252.5(NHERF1):c.81C>T(p.His27His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,450,896 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
Exomes 𝑓: 0.0000062 ( 0 hom. )
Consequence
NHERF1
NM_004252.5 synonymous
NM_004252.5 synonymous
Scores
1
1
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.09
Genes affected
NHERF1 (HGNC:11075): (NHERF family PDZ scaffold protein 1) This gene encodes a sodium/hydrogen exchanger regulatory cofactor. The protein interacts with and regulates various proteins including the cystic fibrosis transmembrane conductance regulator and G-protein coupled receptors such as the beta2-adrenergic receptor and the parathyroid hormone 1 receptor. The protein also interacts with proteins that function as linkers between integral membrane and cytoskeletal proteins. The protein localizes to actin-rich structures including membrane ruffles, microvilli, and filopodia. Mutations in this gene result in hypophosphatemic nephrolithiasis/osteoporosis type 2, and loss of heterozygosity of this gene is implicated in breast cancer.[provided by RefSeq, Sep 2009]
SLC9A3R1-AS1 (HGNC:55322): (SLC9A3R1 antisense RNA 1)
MIR3615 (HGNC:38905): (microRNA 3615) 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 -7 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
BP7
Synonymous conserved (PhyloP=1.1 with no splicing effect.
BS2
High AC in GnomAdExome4 at 9 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NHERF1 | NM_004252.5 | c.81C>T | p.His27His | synonymous_variant | Exon 1 of 6 | ENST00000262613.10 | NP_004243.1 | |
SLC9A3R1-AS1 | NR_187307.1 | n.806G>A | splice_region_variant, non_coding_transcript_exon_variant | Exon 2 of 3 | ||||
MIR3615 | NR_037409.1 | n.*228C>T | downstream_gene_variant | |||||
MIR3615 | unassigned_transcript_3091 | n.*244C>T | downstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NHERF1 | ENST00000262613.10 | c.81C>T | p.His27His | synonymous_variant | Exon 1 of 6 | 1 | NM_004252.5 | ENSP00000262613.5 | ||
NHERF1 | ENST00000583369.5 | c.81C>T | p.His27His | synonymous_variant | Exon 1 of 3 | 3 | ENSP00000464321.1 | |||
SLC9A3R1-AS1 | ENST00000585285.1 | n.-15G>A | upstream_gene_variant | 3 | ||||||
MIR3615 | ENST00000581999.1 | n.*228C>T | downstream_gene_variant | 6 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD3 exomes AF: 0.00000440 AC: 1AN: 227074Hom.: 0 AF XY: 0.00000796 AC XY: 1AN XY: 125632
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GnomAD4 exome AF: 0.00000620 AC: 9AN: 1450896Hom.: 0 Cov.: 32 AF XY: 0.0000111 AC XY: 8AN XY: 721640
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GnomAD4 genome Cov.: 33
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33
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ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
RBP_binding_hub_radar
RBP_regulation_power_radar
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