ENST00000585285.1:n.340+100C>T

Variant names:

• chr17-74748473-G-A
• rs2084313
• ENST00000585285.1:n.340+100C>T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.784

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]

ACMG classification

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-AS1	NR_187307.1	n.1160+100C>T		intron_variant	Intron 2 of 2
NHERF1	NM_004252.5	c.-374G>A		upstream_gene_variant		ENST00000262613.10	NP_004243.1
MIR3615	NR_037409.1	n.-140G>A		upstream_gene_variant
MIR3615	unassigned_transcript_3091	n.-190G>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC9A3R1-AS1	ENST00000585285.1	n.340+100C>T		intron_variant	Intron 1 of 1	3
NHERF1	ENST00000262613.10	c.-374G>A		upstream_gene_variant		1	NM_004252.5	ENSP00000262613.5
NHERF1	ENST00000583369.5	c.-374G>A		upstream_gene_variant		3		ENSP00000464321.1
MIR3615	ENST00000581999.1	n.-140G>A		upstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.0199 AC: 3024 AN: 151804 Hom.: 38 Cov.: 34

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

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

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

Submissions by phenotype

not provided Benign:1

Oct 07, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Other links and lift over

dbSNP: rs2084313; hg19: chr17-72744612;