rs2084313

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr17-74748473-G-A
• chr17-74748473-G-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 38 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000585285.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC9A3R1-AS1	NR_187307.1		n.1160+100C>T		intron	N/A
	NHERF1	NM_004252.5	MANE Select	c.-374G>A		upstream_gene	N/A	NP_004243.1	O14745-1
	MIR3615	NR_037409.1		n.-140G>A		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC9A3R1-AS1	ENST00000585285.1	TSL:3	n.340+100C>T		intron	N/A
	NHERF1	ENST00000262613.10	TSL:1 MANE Select	c.-374G>A		upstream_gene	N/A	ENSP00000262613.5	O14745-1
	NHERF1	ENST00000851804.1		c.-374G>A		upstream_gene	N/A	ENSP00000521863.1

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

African (AFR) AF: 0.0272 AC: 16 AN: 588

American (AMR) AF: 0.0133 AC: 5 AN: 376

Ashkenazi Jewish (ASJ) AF: 0.0441 AC: 27 AN: 612

East Asian (EAS) AF: 0.00 AC: 0 AN: 996

South Asian (SAS) AF: 0.0305 AC: 5 AN: 164

European-Finnish (FIN) AF: 0.0177 AC: 10 AN: 566

Middle Eastern (MID) AF: 0.0543 AC: 5 AN: 92

European-Non Finnish (NFE) AF: 0.0177 AC: 173 AN: 9794

Other (OTH) AF: 0.0266 AC: 26 AN: 978

GnomAD4 genome AF: 0.0199 AC: 3028 AN: 151912 Hom.: 38 Cov.: 34 AF XY: 0.0203 AC XY: 1508 AN XY: 74262

African (AFR) AF: 0.0210 AC: 872 AN: 41482

American (AMR) AF: 0.0262 AC: 400 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0412 AC: 143 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5136

South Asian (SAS) AF: 0.0352 AC: 170 AN: 4830

European-Finnish (FIN) AF: 0.0193 AC: 203 AN: 10540

Middle Eastern (MID) AF: 0.0548 AC: 16 AN: 292

European-Non Finnish (NFE) AF: 0.0173 AC: 1171 AN: 67868

Other (OTH) AF: 0.0237 AC: 50 AN: 2106

Alfa AF: 0.00556 Hom.: 0

Bravo AF: 0.0198

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	6.8
DANN	Benign	0.89
PhyloP100		-0.78
PromoterAI		-0.018	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2084313; hg19: chr17-72744612;