rs112064121

Variant names:

• chrX-50069627-C-G
• rs112064121
• ENST00000307367.2:c.-165C>G

Your query was ambiguous. Multiple possible variants found:

• chrX-50069627-C-G
• chrX-50069627-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001282163.2(CLCN5):​c.-105C>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 NM_001282163.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.306
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• Dent disease type 1

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282163.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLCN5	NM_001127898.4	MANE Select	c.164-252C>G		intron	N/A	NP_001121370.1	P51795-2
	CLCN5	NM_001282163.2		c.-105C>G		5_prime_UTR	Exon 1 of 12	NP_001269092.1
	CLCN5	NM_001440756.1		c.176-252C>G		intron	N/A	NP_001427685.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLCN5	ENST00000307367.2	TSL:1	c.-165C>G		5_prime_UTR	Exon 1 of 12	ENSP00000304257.2	P51795-1
	CLCN5	ENST00000376091.8	TSL:2 MANE Select	c.164-252C>G		intron	N/A	ENSP00000365259.3	P51795-2
	CLCN5	ENST00000376108.7	TSL:1	c.-47-252C>G		intron	N/A	ENSP00000365276.3	P51795-1

Frequencies

GnomAD3 genomes AF: 0.0572 AC: 6364 AN: 111163 Hom.: 497 Cov.: 23

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

African (AFR) AF: 0.209 AC: 3628 AN: 17330

American (AMR) AF: 0.0139 AC: 92 AN: 6597

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9087

East Asian (EAS) AF: 0.00 AC: 0 AN: 15511

South Asian (SAS) AF: 0.000182 AC: 3 AN: 16523

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9971

Middle Eastern (MID) AF: 0.00912 AC: 16 AN: 1755

European-Non Finnish (NFE) AF: 0.000140 AC: 95 AN: 679498

Other (OTH) AF: 0.0126 AC: 393 AN: 31246

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

African (AFR) AF: 0.199 AC: 6076 AN: 30465

American (AMR) AF: 0.0197 AC: 206 AN: 10437

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2638

East Asian (EAS) AF: 0.00 AC: 0 AN: 3533

South Asian (SAS) AF: 0.000767 AC: 2 AN: 2609

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6041

Middle Eastern (MID) AF: 0.00463 AC: 1 AN: 216

European-Non Finnish (NFE) AF: 0.000509 AC: 27 AN: 53075

Other (OTH) AF: 0.0323 AC: 49 AN: 1516

Alfa AF: 0.0459 Hom.: 156

Bravo AF: 0.0652

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.2
DANN	Benign	0.39
PhyloP100		0.31
PromoterAI		-0.0059	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs112064121; hg19: chrX-49834282;