Variant X-50067546-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0840

Variant links:

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]

CLCN5 links:

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ACMG classification

Classification made for transcript

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 linkuse as main transcript	c.164-2333T>G		intron_variant		ENST00000376091.8	NP_001121370.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
CLCN5	ENST00000376091.8 linkuse as main transcript	c.164-2333T>G	intron_variant	2	NM_001127898.4	ENSP00000365259	P3	P51795-2
CLCN5	ENST00000376088.7 linkuse as main transcript	c.164-2333T>G	intron_variant	2		ENSP00000365256	P3	P51795-2
CLCN5	ENST00000643129.1 linkuse as main transcript	c.*261-2333T>G	intron_variant, NMD_transcript_variant			ENSP00000496056
CLCN5	ENST00000376108.7 linkuse as main transcript		upstream_gene_variant	1		ENSP00000365276	A1	P51795-1

Frequencies

GnomAD3 genomes

AF:

0.000593

AC:

AN:

111257

Hom.:

Cov.:

AF XY:

0.000508

AC XY:

AN XY:

33451

show subpopulations

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.:

Cov.:

AF XY:

0.000508

AC XY:

AN XY:

181181

show subpopulations

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:

AN:

111310

Hom.:

Cov.:

AF XY:

0.000507

AC XY:

AN XY:

33514

show subpopulations

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.:

Bravo

AF:

0.000533

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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

DANN

Benign

0.62

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over