17-74748444-A-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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=-0.82).
• 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-AS1	NR_187307.1	n.1160+129T>G		intron_variant	Intron 2 of 2
NHERF1	NM_004252.5	c.-403A>C		upstream_gene_variant		ENST00000262613.10	NP_004243.1
MIR3615	NR_037409.1	n.-169A>C		upstream_gene_variant
MIR3615	unassigned_transcript_3091	n.-219A>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC9A3R1-AS1	ENST00000585285.1	n.340+129T>G		intron_variant	Intron 1 of 1	3
NHERF1	ENST00000262613.10	c.-403A>C		upstream_gene_variant		1	NM_004252.5	ENSP00000262613.5
NHERF1	ENST00000583369.5	c.-403A>C		upstream_gene_variant		3		ENSP00000464321.1
MIR3615	ENST00000581999.1	n.-169A>C		upstream_gene_variant		6

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

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

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

Submissions by phenotype

not provided Benign:1

Oct 16, 2018

GeneDx

Significance: 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	-0.82
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

Other links and lift over

dbSNP: rs2384953; hg19: chr17-72744583;