X-50072195-G-T

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.316-294G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00918 in 111,892 control chromosomes in the GnomAD database, including 5 homozygotes. There are 271 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 0.0092 (5 hom., 271 hem., cov: 23)
• Consequence: CLCN5 NM_001127898.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.75

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=-0.84).
• BP6: Variant X-50072195-G-T is Benign according to our data. Variant chrX-50072195-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1223211.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00918 (1027/111892) while in subpopulation NFE AF= 0.015 (799/53129). AF 95% confidence interval is 0.0142. There are 5 homozygotes in gnomad4. There are 271 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 5 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLCN5	NM_001127898.4	c.316-294G>T		intron_variant		ENST00000376091.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLCN5	ENST00000376091.8	c.316-294G>T		intron_variant		2	NM_001127898.4	P3

Frequencies

GnomAD3 genomes AF: 0.00918 AC: 1027 AN: 111839 Hom.: 5 Cov.: 23 AF XY: 0.00797 AC XY: 271 AN XY: 34017

Gnomad AFR AF: 0.00192

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0118

Gnomad ASJ AF: 0.00870

Gnomad EAS AF: 0.000278

Gnomad SAS AF: 0.00111

Gnomad FIN AF: 0.000825

Gnomad MID AF: 0.00417

Gnomad NFE AF: 0.0150

Gnomad OTH AF: 0.00798

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00918 AC: 1027 AN: 111892 Hom.: 5 Cov.: 23 AF XY: 0.00795 AC XY: 271 AN XY: 34080

Gnomad4 AFR AF: 0.00191

Gnomad4 AMR AF: 0.0118

Gnomad4 ASJ AF: 0.00870

Gnomad4 EAS AF: 0.000278

Gnomad4 SAS AF: 0.00111

Gnomad4 FIN AF: 0.000825

Gnomad4 NFE AF: 0.0150

Gnomad4 OTH AF: 0.00788

Alfa AF: 0.00935 Hom.: 49

Bravo AF: 0.00929

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

Jun 06, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	3.2
Dann	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs150785487; hg19: chrX-49836850;