chr17-74748473-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000585285.1(SLC9A3R1-AS1):​n.340+100C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0198 in 166,078 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.020 ( 38 hom., cov: 34)
Exomes 𝑓: 0.019 ( 5 hom. )

Consequence

SLC9A3R1-AS1
ENST00000585285.1 intron

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.784
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=-0.73).
BP6
Variant 17-74748473-G-A is Benign according to our data. Variant chr17-74748473-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1316461.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0199 (3028/151912) while in subpopulation SAS AF= 0.0352 (170/4830). AF 95% confidence interval is 0.0309. There are 38 homozygotes in gnomad4. There are 1508 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 38 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC9A3R1-AS1NR_187307.1 linkn.1160+100C>T intron_variant Intron 2 of 2
NHERF1NM_004252.5 linkc.-374G>A upstream_gene_variant ENST00000262613.10 NP_004243.1 O14745-1
MIR3615NR_037409.1 linkn.-140G>A upstream_gene_variant
MIR3615unassigned_transcript_3091 n.-190G>A upstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC9A3R1-AS1ENST00000585285.1 linkn.340+100C>T intron_variant Intron 1 of 1 3
NHERF1ENST00000262613.10 linkc.-374G>A upstream_gene_variant 1 NM_004252.5 ENSP00000262613.5 O14745-1
NHERF1ENST00000583369.5 linkc.-374G>A upstream_gene_variant 3 ENSP00000464321.1 J3QRP6
MIR3615ENST00000581999.1 linkn.-140G>A upstream_gene_variant 6

Frequencies

GnomAD3 genomes
AF:
0.0199
AC:
3024
AN:
151804
Hom.:
38
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0210
Gnomad AMI
AF:
0.00329
Gnomad AMR
AF:
0.0262
Gnomad ASJ
AF:
0.0412
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.0350
Gnomad FIN
AF:
0.0193
Gnomad MID
AF:
0.0510
Gnomad NFE
AF:
0.0173
Gnomad OTH
AF:
0.0240
GnomAD4 exome
AF:
0.0188
AC:
267
AN:
14166
Hom.:
5
AF XY:
0.0221
AC XY:
158
AN XY:
7160
show subpopulations
Gnomad4 AFR exome
AF:
0.0272
Gnomad4 AMR exome
AF:
0.0133
Gnomad4 ASJ exome
AF:
0.0441
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0305
Gnomad4 FIN exome
AF:
0.0177
Gnomad4 NFE exome
AF:
0.0177
Gnomad4 OTH exome
AF:
0.0266
GnomAD4 genome
AF:
0.0199
AC:
3028
AN:
151912
Hom.:
38
Cov.:
34
AF XY:
0.0203
AC XY:
1508
AN XY:
74262
show subpopulations
Gnomad4 AFR
AF:
0.0210
Gnomad4 AMR
AF:
0.0262
Gnomad4 ASJ
AF:
0.0412
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.0352
Gnomad4 FIN
AF:
0.0193
Gnomad4 NFE
AF:
0.0173
Gnomad4 OTH
AF:
0.0237
Alfa
AF:
0.00556
Hom.:
0
Bravo
AF:
0.0198

ClinVar

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

Submissions by phenotype

not provided Benign:1
Oct 07, 2019
GeneDx
Significance: Likely 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
-0.73
CADD
Benign
6.8
DANN
Benign
0.89

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: rs2084313; hg19: chr17-72744612; API