chrX-50042261-G-A

Position:

• chrX-50042261-G-A

Variant summary

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

The NM_001127898.4(CLCN5):​c.17-55G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 621,999 control chromosomes in the GnomAD database, including 2 homozygotes. There are 143 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0035 (1 hom., 99 hem., cov: 23)
  • Exomes 𝑓: 0.00047 (1 hom. 44 hem.)
• Consequence: CLCN5 NM_001127898.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.580

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant X-50042261-G-A is Benign according to our data. Variant chrX-50042261-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1215662.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00346 (387/111741) while in subpopulation AFR AF= 0.0122 (374/30777). AF 95% confidence interval is 0.0111. There are 1 homozygotes in gnomad4. There are 99 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd4 at 99 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLCN5	NM_001127898.4	c.17-55G>A		intron_variant		ENST00000376091.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLCN5	ENST00000376091.8	c.17-55G>A		intron_variant		2	NM_001127898.4	P3
CLCN5	ENST00000376088.7	c.17-55G>A		intron_variant		2		P3
CLCN5	ENST00000482218.2	c.17-55G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.00347 AC: 387 AN: 111685 Hom.: 1 Cov.: 23 AF XY: 0.00292 AC XY: 99 AN XY: 33871

Gnomad AFR AF: 0.0122

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000854

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000377

Gnomad OTH AF: 0.00133

GnomAD4 exome AF: 0.000470 AC: 240 AN: 510258 Hom.: 1 AF XY: 0.000357 AC XY: 44 AN XY: 123290

Gnomad4 AFR exome AF: 0.0156

Gnomad4 AMR exome AF: 0.000258

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000300

Gnomad4 NFE exome AF: 0.0000162

Gnomad4 OTH exome AF: 0.00119

GnomAD4 genome AF: 0.00346 AC: 387 AN: 111741 Hom.: 1 Cov.: 23 AF XY: 0.00292 AC XY: 99 AN XY: 33937

Gnomad4 AFR AF: 0.0122

Gnomad4 AMR AF: 0.000853

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000377

Gnomad4 OTH AF: 0.00132

Bravo AF: 0.00427

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.12
DANN	Benign	0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs183862468; hg19: chrX-49806870;