rs456617

Variant names:

• chrX-50003229-G-A
• rs456617
• NM_001127898.4:c.17-39087G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-50003229-G-A
• chrX-50003229-G-C
• chrX-50003229-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001127898.4(CLCN5):​c.17-39087G>A variant causes a intron change. The variant allele was found at a frequency of 0.00000371 in 269,611 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000037 (0 hom. 1 hem.)
• Consequence: CLCN5 NM_001127898.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.61
• Publications: 10 publications found

Genes affected

CLCN5 (HGNC:2023): (chloride voltage-gated channel 5) This gene encodes a member of the ClC family of chloride ion channels and ion transporters. The encoded protein is primarily localized to endosomal membranes and may function to facilitate albumin uptake by the renal proximal tubule. Mutations in this gene have been found in Dent disease and renal tubular disorders complicated by nephrolithiasis. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2013]

MIR532 (HGNC:32795): (microRNA 532) 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (Cadd=17.76).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001127898.4. 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
	CLCN5	NM_001127898.4	MANE Select	c.17-39087G>A		intron	N/A	NP_001121370.1	P51795-2
	CLCN5	NM_001440756.1		c.17-39087G>A		intron	N/A	NP_001427685.1
	CLCN5	NM_001440757.1		c.17-39087G>A		intron	N/A	NP_001427686.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLCN5	ENST00000376091.8	TSL:2 MANE Select	c.17-39087G>A		intron	N/A	ENSP00000365259.3	P51795-2
	CLCN5	ENST00000376088.7	TSL:2	c.17-39087G>A		intron	N/A	ENSP00000365256.3	P51795-2
	CLCN5	ENST00000854414.1		c.17-39087G>A		intron	N/A	ENSP00000524473.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000371 AC: 1 AN: 269611 Hom.: 0 Cov.: 0 AF XY: 0.00000945 AC XY: 1 AN XY: 105875

African (AFR) AF: 0.00 AC: 0 AN: 8364

American (AMR) AF: 0.00 AC: 0 AN: 28658

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8647

East Asian (EAS) AF: 0.00 AC: 0 AN: 9747

South Asian (SAS) AF: 0.00 AC: 0 AN: 39433

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21878

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2030

European-Non Finnish (NFE) AF: 0.00000722 AC: 1 AN: 138582

Other (OTH) AF: 0.00 AC: 0 AN: 12272

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
CADD	Benign	18
PhyloP100		3.6

Splicing

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

Other links and lift over

dbSNP: rs456617;