X-50067578-G-A

Position:

• chrX-50067578-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The ENST00000376108.7(CLCN5):​c.-230G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000797 in 751,643 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 189 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 0.00064 (0 hom., 20 hem., cov: 23)
  • Exomes 𝑓: 0.00082 (0 hom. 169 hem.)
• Consequence: CLCN5 ENST00000376108.7 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.34

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP6: Variant X-50067578-G-A is Benign according to our data. Variant chrX-50067578-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 368470.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000644 (72/111744) while in subpopulation AMR AF= 0.00258 (27/10485). AF 95% confidence interval is 0.00182. There are 0 homozygotes in gnomad4. There are 20 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd4 at 20 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLCN5	NM_001127898.4	c.164-2301G>A		intron_variant		ENST00000376091.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLCN5	ENST00000376108.7	c.-230G>A		5_prime_UTR_variant	1/12	1		A1
CLCN5	ENST00000376091.8	c.164-2301G>A		intron_variant		2	NM_001127898.4	P3
CLCN5	ENST00000376088.7	c.164-2301G>A		intron_variant		2		P3
CLCN5	ENST00000643129.1	c.*261-2301G>A		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.000645 AC: 72 AN: 111691 Hom.: 0 Cov.: 23 AF XY: 0.000590 AC XY: 20 AN XY: 33891

Gnomad AFR AF: 0.0000325

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00258

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0210

Gnomad NFE AF: 0.000677

Gnomad OTH AF: 0.00201

GnomAD4 exome AF: 0.000824 AC: 527 AN: 639899 Hom.: 0 Cov.: 18 AF XY: 0.000882 AC XY: 169 AN XY: 191517

Gnomad4 AFR exome AF: 0.000403

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000868

Gnomad4 OTH exome AF: 0.000473

GnomAD4 genome AF: 0.000644 AC: 72 AN: 111744 Hom.: 0 Cov.: 23 AF XY: 0.000589 AC XY: 20 AN XY: 33954

Gnomad4 AFR AF: 0.0000325

Gnomad4 AMR AF: 0.00258

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000677

Gnomad4 OTH AF: 0.00198

Alfa AF: 0.000498 Hom.: 1

Bravo AF: 0.00111

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Dent disease Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	19
DANN	Benign	0.94

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: rs781805006; hg19: chrX-49832233;