chr1-11840768-G-A

Position:

• chr1-11840768-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001286.5(CLCN6):​c.*545G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• 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:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLCN6	ENST00000346436.11	c.*545G>A		3_prime_UTR_variant	23/23	1	NM_001286.5	ENSP00000234488.9
CLCN6	ENST00000312413.10	c.*545G>A		3_prime_UTR_variant	22/22	2		ENSP00000308367.7
CLCN6	ENST00000400892.3	n.*1252-290G>A		intron_variant		3		ENSP00000496938.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.77
DANN	Benign	0.92

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;