rs2384953

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000585285.1(SLC9A3R1-AS1):​n.340+129T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 156,114 control chromosomes in the GnomAD database, including 17,850 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.47 ( 17322 hom., cov: 32)
Exomes 𝑓: 0.48 ( 528 hom. )

Consequence

SLC9A3R1-AS1
ENST00000585285.1 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.761
Variant links:
Genes affected
SLC9A3R1-AS1 (HGNC:55322): (SLC9A3R1 antisense RNA 1)
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]
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 -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 17-74748444-A-C is Benign according to our data. Variant chr17-74748444-A-C is described in ClinVar as [Benign]. Clinvar id is 1247073.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC9A3R1-AS1NR_187307.1 linkn.1160+129T>G intron_variant Intron 2 of 2
NHERF1NM_004252.5 linkc.-403A>C upstream_gene_variant ENST00000262613.10 NP_004243.1 O14745-1
MIR3615NR_037409.1 linkn.-169A>C upstream_gene_variant
MIR3615unassigned_transcript_3091 n.-219A>C upstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC9A3R1-AS1ENST00000585285.1 linkn.340+129T>G intron_variant Intron 1 of 1 3
NHERF1ENST00000262613.10 linkc.-403A>C upstream_gene_variant 1 NM_004252.5 ENSP00000262613.5 O14745-1
NHERF1ENST00000583369.5 linkc.-403A>C upstream_gene_variant 3 ENSP00000464321.1 J3QRP6
MIR3615ENST00000581999.1 linkn.-169A>C upstream_gene_variant 6

Frequencies

GnomAD3 genomes
AF:
0.472
AC:
71478
AN:
151438
Hom.:
17290
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.376
Gnomad AMI
AF:
0.313
Gnomad AMR
AF:
0.489
Gnomad ASJ
AF:
0.464
Gnomad EAS
AF:
0.448
Gnomad SAS
AF:
0.422
Gnomad FIN
AF:
0.571
Gnomad MID
AF:
0.442
Gnomad NFE
AF:
0.520
Gnomad OTH
AF:
0.456
GnomAD4 exome
AF:
0.485
AC:
2214
AN:
4568
Hom.:
528
AF XY:
0.484
AC XY:
1137
AN XY:
2348
show subpopulations
Gnomad4 AFR exome
AF:
0.380
Gnomad4 AMR exome
AF:
0.523
Gnomad4 ASJ exome
AF:
0.413
Gnomad4 EAS exome
AF:
0.453
Gnomad4 SAS exome
AF:
0.403
Gnomad4 FIN exome
AF:
0.574
Gnomad4 NFE exome
AF:
0.492
Gnomad4 OTH exome
AF:
0.483
GnomAD4 genome
AF:
0.472
AC:
71553
AN:
151546
Hom.:
17322
Cov.:
32
AF XY:
0.474
AC XY:
35141
AN XY:
74106
show subpopulations
Gnomad4 AFR
AF:
0.376
Gnomad4 AMR
AF:
0.489
Gnomad4 ASJ
AF:
0.464
Gnomad4 EAS
AF:
0.448
Gnomad4 SAS
AF:
0.422
Gnomad4 FIN
AF:
0.571
Gnomad4 NFE
AF:
0.520
Gnomad4 OTH
AF:
0.461
Alfa
AF:
0.411
Hom.:
1848
Bravo
AF:
0.468
Asia WGS
AF:
0.394
AC:
1339
AN:
3394

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Oct 16, 2018
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
9.6
DANN
Benign
0.32

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2384953; hg19: chr17-72744583; API