chr1-11840768-G-T

Variant names:

• chr1-11840768-G-T
• rs198414
• NM_001286.5:c.*545G>T

Variant summary

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

The NM_001286.5(CLCN6):​c.*545G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 171,272 control chromosomes in the GnomAD database, including 3,916 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 0.19 (3745 hom., cov: 33)
  • Exomes 𝑓: 0.12 (171 hom.)
• Consequence: CLCN6 NM_001286.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.22

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:37635): (NPPA antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLCN6	NM_001286.5	c.*545G>T		3_prime_UTR_variant	Exon 23 of 23	ENST00000346436.11	NP_001277.2
CLCN6	NM_001256959.2	c.*545G>T		3_prime_UTR_variant	Exon 22 of 22		NP_001243888.2
NPPA-AS1	NR_037806.1	n.450G>T		non_coding_transcript_exon_variant	Exon 1 of 4
CLCN6	NR_046428.2	n.3211G>T		non_coding_transcript_exon_variant	Exon 23 of 23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLCN6	ENST00000346436.11	c.*545G>T		3_prime_UTR_variant	Exon 23 of 23	1	NM_001286.5	ENSP00000234488.9
CLCN6	ENST00000312413.10	c.*545G>T		3_prime_UTR_variant	Exon 22 of 22	2		ENSP00000308367.7
CLCN6	ENST00000400892.3	n.*1252-290G>T		intron_variant	Intron 23 of 26	3		ENSP00000496938.1
CLCN6	ENST00000446542.5	n.-249G>T		upstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29013 AN: 151962 Hom.: 3739 Cov.: 33

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.0104

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.0723

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.189

GnomAD4 exome AF: 0.121 AC: 2331 AN: 19192 Hom.: 171 Cov.: 0 AF XY: 0.120 AC XY: 1191 AN XY: 9940

Gnomad4 AFR exome AF: 0.323

Gnomad4 AMR exome AF: 0.105

Gnomad4 ASJ exome AF: 0.0871

Gnomad4 EAS exome AF: 0.00828

Gnomad4 SAS exome AF: 0.143

Gnomad4 FIN exome AF: 0.0719

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.133

GnomAD4 genome AF: 0.191 AC: 29044 AN: 152080 Hom.: 3745 Cov.: 33 AF XY: 0.188 AC XY: 13999 AN XY: 74330

Gnomad4 AFR AF: 0.363

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.0104

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.0723

Gnomad4 NFE AF: 0.140

Gnomad4 OTH AF: 0.190

Alfa AF: 0.147 Hom.: 2544

Bravo AF: 0.202

Asia WGS AF: 0.0960 AC: 334 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.62
DANN	Benign	0.47

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: rs198414; hg19: chr1-11900825;