rs17350396

Positions:

• chr1-11840781-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001286.5(CLCN6):​c.*558A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 167,990 control chromosomes in the GnomAD database, including 1,630 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.12 (1460 hom., cov: 32)
  • Exomes 𝑓: 0.13 (170 hom.)
• Consequence: CLCN6 NM_001286.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18

Genes affected

CLCN6 (HGNC:2024): (chloride voltage-gated channel 6) This gene encodes a member of the voltage-dependent chloride channel protein family. Members of this family can function as either chloride channels or antiporters. This protein is primarily localized to late endosomes and functions as a chloride/proton antiporter. Alternate splicing results in both coding and non-coding variants. Additional alternately spliced variants have been described but their full-length structure is unknown. [provided by RefSeq, Mar 2012]

NPPA-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLCN6	NM_001286.5	c.*558A>G		3_prime_UTR_variant	23/23	ENST00000346436.11	NP_001277.2
CLCN6	NM_001256959.2	c.*558A>G		3_prime_UTR_variant	22/22		NP_001243888.2
NPPA-AS1	NR_037806.1	n.463A>G		non_coding_transcript_exon_variant	1/4
CLCN6	NR_046428.2	n.3224A>G		non_coding_transcript_exon_variant	23/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLCN6	ENST00000346436.11	c.*558A>G		3_prime_UTR_variant	23/23	1	NM_001286.5	ENSP00000234488.9
CLCN6	ENST00000312413.10	c.*558A>G		3_prime_UTR_variant	22/22	2		ENSP00000308367.7
CLCN6	ENST00000400892.3	n.*1252-277A>G		intron_variant		3		ENSP00000496938.1

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18739 AN: 152082 Hom.: 1463 Cov.: 32

Gnomad AFR AF: 0.0315

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.0993

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.0975

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.142

GnomAD4 exome AF: 0.125 AC: 1981 AN: 15790 Hom.: 170 Cov.: 0 AF XY: 0.134 AC XY: 1108 AN XY: 8274

Gnomad4 AFR exome AF: 0.0224

Gnomad4 AMR exome AF: 0.0951

Gnomad4 ASJ exome AF: 0.133

Gnomad4 EAS exome AF: 0.0846

Gnomad4 SAS exome AF: 0.208

Gnomad4 FIN exome AF: 0.125

Gnomad4 NFE exome AF: 0.137

Gnomad4 OTH exome AF: 0.120

GnomAD4 genome AF: 0.123 AC: 18731 AN: 152200 Hom.: 1460 Cov.: 32 AF XY: 0.124 AC XY: 9192 AN XY: 74394

Gnomad4 AFR AF: 0.0314

Gnomad4 AMR AF: 0.0992

Gnomad4 ASJ AF: 0.196

Gnomad4 EAS AF: 0.0975

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.169

Gnomad4 NFE AF: 0.168

Gnomad4 OTH AF: 0.141

Alfa AF: 0.162 Hom.: 2904

Bravo AF: 0.113

Asia WGS AF: 0.151 AC: 525 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.32
DANN	Benign	0.36

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: rs17350396; hg19: chr1-11900838; COSMIC: COSV56738901; COSMIC: COSV56738901;