X-50069627-C-G

Position:

• chrX-50069627-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000307367.2(CLCN5):​c.-165C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0118 in 898,734 control chromosomes in the GnomAD database, including 812 homozygotes. There are 2,656 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.057 (497 hom., 1665 hem., cov: 23)
  • Exomes 𝑓: 0.0054 (315 hom. 991 hem.)
• Consequence: CLCN5 ENST00000307367.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.306

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant X-50069627-C-G is Benign according to our data. Variant chrX-50069627-C-G is described in ClinVar as [Benign]. Clinvar id is 1245383.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLCN5	NM_001127898.4	c.164-252C>G		intron_variant		ENST00000376091.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLCN5	ENST00000376091.8	c.164-252C>G		intron_variant		2	NM_001127898.4	P3

Frequencies

GnomAD3 genomes AF: 0.0572 AC: 6364 AN: 111163 Hom.: 497 Cov.: 23 AF XY: 0.0499 AC XY: 1667 AN XY: 33397

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000765

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00422

Gnomad NFE AF: 0.000509

Gnomad OTH AF: 0.0327

GnomAD4 exome AF: 0.00537 AC: 4227 AN: 787518 Hom.: 315 Cov.: 23 AF XY: 0.00444 AC XY: 991 AN XY: 223054

Gnomad4 AFR exome AF: 0.209

Gnomad4 AMR exome AF: 0.0139

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000182

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000140

Gnomad4 OTH exome AF: 0.0126

GnomAD4 genome AF: 0.0572 AC: 6361 AN: 111216 Hom.: 497 Cov.: 23 AF XY: 0.0498 AC XY: 1665 AN XY: 33460

Gnomad4 AFR AF: 0.199

Gnomad4 AMR AF: 0.0197

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000767

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000509

Gnomad4 OTH AF: 0.0323

Alfa AF: 0.0459 Hom.: 156

Bravo AF: 0.0652

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 18, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.2
DANN	Benign	0.39

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: rs112064121; hg19: chrX-49834282;