chrX-50067546-T-G

Position:

• chrX-50067546-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001127898.4(CLCN5):​c.164-2333T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000605 in 739,353 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 109 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 0.00059 (0 hom., 17 hem., cov: 22)
  • Exomes 𝑓: 0.00061 (0 hom. 92 hem.)
• Consequence: CLCN5 NM_001127898.4 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0840

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=-0.73).
• BP6: Variant X-50067546-T-G is Benign according to our data. Variant chrX-50067546-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 369638.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000593 (66/111310) while in subpopulation NFE AF= 0.000904 (48/53088). AF 95% confidence interval is 0.0007. There are 0 homozygotes in gnomad4. There are 17 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd4 at 17 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLCN5	NM_001127898.4	c.164-2333T>G		intron_variant		ENST00000376091.8	NP_001121370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLCN5	ENST00000376091.8	c.164-2333T>G		intron_variant		2	NM_001127898.4	ENSP00000365259	P3
CLCN5	ENST00000376088.7	c.164-2333T>G		intron_variant		2		ENSP00000365256	P3
CLCN5	ENST00000643129.1	c.*261-2333T>G		intron_variant, NMD_transcript_variant				ENSP00000496056
CLCN5	ENST00000376108.7			upstream_gene_variant		1		ENSP00000365276	A1

Frequencies

GnomAD3 genomes AF: 0.000593 AC: 66 AN: 111257 Hom.: 0 Cov.: 22 AF XY: 0.000508 AC XY: 17 AN XY: 33451

Gnomad AFR AF: 0.0000327

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000770

Gnomad ASJ AF: 0.00227

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000382

Gnomad FIN AF: 0.000167

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000904

Gnomad OTH AF: 0.000670

GnomAD4 exome AF: 0.000607 AC: 381 AN: 628043 Hom.: 0 Cov.: 11 AF XY: 0.000508 AC XY: 92 AN XY: 181181

Gnomad4 AFR exome AF: 0.0000821

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00180

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000256

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000630

Gnomad4 OTH exome AF: 0.000386

GnomAD4 genome AF: 0.000593 AC: 66 AN: 111310 Hom.: 0 Cov.: 22 AF XY: 0.000507 AC XY: 17 AN XY: 33514

Gnomad4 AFR AF: 0.0000326

Gnomad4 AMR AF: 0.000769

Gnomad4 ASJ AF: 0.00227

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000384

Gnomad4 FIN AF: 0.000167

Gnomad4 NFE AF: 0.000904

Gnomad4 OTH AF: 0.000661

Alfa AF: 0.00146 Hom.: 8

Bravo AF: 0.000533

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Dent disease Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	12
DANN	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs41310663; hg19: chrX-49832201;