ENST00000585285.1:n.340+129T>G

Variant names:

• chr17-74748444-A-C
• rs2384953
• ENST00000585285.1:n.340+129T>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.761
• Publications: 5 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=-0.82).
• BP6: Variant 17-74748444-A-C is Benign according to our data. Variant chr17-74748444-A-C is described in ClinVar as Benign. ClinVar VariationId 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.

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+129T>G		intron	N/A
	NHERF1	NM_004252.5	MANE Select	c.-403A>C		upstream_gene	N/A	NP_004243.1	O14745-1
	MIR3615	NR_037409.1		n.-169A>C		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+129T>G		intron	N/A
	NHERF1	ENST00000262613.10	TSL:1 MANE Select	c.-403A>C		upstream_gene	N/A	ENSP00000262613.5	O14745-1
	NHERF1	ENST00000851804.1		c.-403A>C		upstream_gene	N/A	ENSP00000521863.1

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71478 AN: 151438 Hom.: 17290 Cov.: 32

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

African (AFR) AF: 0.380 AC: 70 AN: 184

American (AMR) AF: 0.523 AC: 68 AN: 130

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 81 AN: 196

East Asian (EAS) AF: 0.453 AC: 97 AN: 214

South Asian (SAS) AF: 0.403 AC: 29 AN: 72

European-Finnish (FIN) AF: 0.574 AC: 93 AN: 162

Middle Eastern (MID) AF: 0.531 AC: 17 AN: 32

European-Non Finnish (NFE) AF: 0.492 AC: 1614 AN: 3278

Other (OTH) AF: 0.483 AC: 145 AN: 300

GnomAD4 genome AF: 0.472 AC: 71553 AN: 151546 Hom.: 17322 Cov.: 32 AF XY: 0.474 AC XY: 35141 AN XY: 74106

African (AFR) AF: 0.376 AC: 15571 AN: 41364

American (AMR) AF: 0.489 AC: 7463 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 1609 AN: 3470

East Asian (EAS) AF: 0.448 AC: 2279 AN: 5088

South Asian (SAS) AF: 0.422 AC: 2030 AN: 4816

European-Finnish (FIN) AF: 0.571 AC: 5996 AN: 10494

Middle Eastern (MID) AF: 0.421 AC: 122 AN: 290

European-Non Finnish (NFE) AF: 0.520 AC: 35230 AN: 67766

Other (OTH) AF: 0.461 AC: 969 AN: 2104

Alfa AF: 0.451 Hom.: 4779

Bravo AF: 0.468

Asia WGS AF: 0.394 AC: 1339 AN: 3394

ClinVar

ClinVar submissions

Significance: 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	-0.82
CADD	Benign	9.6
DANN	Benign	0.32
PhyloP100		-0.76
PromoterAI		-0.031	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2384953; hg19: chr17-72744583;