1-11846856-C-T
Variant names:
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_006172.4(NPPA):c.450+257G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000199 in 150,974 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000020 ( 0 hom., cov: 28)
Consequence
NPPA
NM_006172.4 intron
NM_006172.4 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -2.31
Genes affected
NPPA (HGNC:7939): (natriuretic peptide A) The protein encoded by this gene belongs to the natriuretic peptide family. Natriuretic peptides are implicated in the control of extracellular fluid volume and electrolyte homeostasis. This protein is synthesized as a large precursor (containing a signal peptide), which is processed to release a peptide from the N-terminus with similarity to vasoactive peptide, cardiodilatin, and another peptide from the C-terminus with natriuretic-diuretic activity. Mutations in this gene have been associated with atrial fibrillation familial type 6. This gene is located adjacent to another member of the natriuretic family of peptides on chromosome 1. [provided by RefSeq, Oct 2015]
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]
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ACMG classification
Classification made for transcript
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=-1.06).
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| NPPA | ENST00000376480.7 | c.450+257G>A | intron_variant | Intron 2 of 2 | 1 | NM_006172.4 | ENSP00000365663.3 | |||
| CLCN6 | ENST00000446542.5 | n.782-578C>T | intron_variant | Intron 3 of 3 | 1 | |||||
| NPPA | ENST00000376476.1 | c.300+257G>A | intron_variant | Intron 2 of 2 | 3 | ENSP00000365659.1 | ||||
| CLCN6 | ENST00000400892.3 | n.*1962-721C>T | intron_variant | Intron 26 of 26 | 3 | ENSP00000496938.1 |
Frequencies
GnomAD3 genomes 0.0000199 AC: 3AN: 150974Hom.: 0 Cov.: 28
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome 0.0000199 AC: 3AN: 150974Hom.: 0 Cov.: 28 AF XY: 0.0000136 AC XY: 1AN XY: 73700
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ClinVar
Not reported inComputational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at