rs13306560
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4BP6_ModerateBA1
The ENST00000312413.10(CLCN6):c.-137C>T variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.0455 in 640,040 control chromosomes in the GnomAD database, including 792 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.037 ( 153 hom., cov: 33)
Exomes 𝑓: 0.048 ( 639 hom. )
Consequence
CLCN6
ENST00000312413.10 5_prime_UTR
ENST00000312413.10 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.66
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]
MTHFR (HGNC:7436): (methylenetetrahydrofolate reductase) The protein encoded by this gene catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a co-substrate for homocysteine remethylation to methionine. Genetic variation in this gene influences susceptibility to occlusive vascular disease, neural tube defects, colon cancer and acute leukemia, and mutations in this gene are associated with methylenetetrahydrofolate reductase deficiency.[provided by RefSeq, Oct 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.14).
BP6
?
Variant 1-11806126-C-T is Benign according to our data. Variant chr1-11806126-C-T is described in ClinVar as [Benign]. Clinvar id is 1170440.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0528 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CLCN6 | ENST00000312413.10 | c.-137C>T | 5_prime_UTR_variant | 1/22 | 2 | ||||
MTHFR | ENST00000641747.1 | c.-252G>A | 5_prime_UTR_variant, NMD_transcript_variant | 1/11 | |||||
MTHFR | ENST00000642002.1 | upstream_gene_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0371 AC: 5643AN: 152200Hom.: 151 Cov.: 33
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GnomAD4 exome AF: 0.0481 AC: 23475AN: 487722Hom.: 639 Cov.: 7 AF XY: 0.0483 AC XY: 11711AN XY: 242544
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GnomAD4 genome ? AF: 0.0371 AC: 5648AN: 152318Hom.: 153 Cov.: 33 AF XY: 0.0371 AC XY: 2762AN XY: 74480
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Homocystinuria due to methylene tetrahydrofolate reductase deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 12, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at