1-11847093-C-T
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate
The ENST00000376480.7(NPPA):c.450+20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000396 in 1,516,924 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000037 ( 0 hom. )
Consequence
NPPA
ENST00000376480.7 intron
ENST00000376480.7 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.777
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 -6 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
Variant 1-11847093-C-T is Benign according to our data. Variant chr1-11847093-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2715969.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NPPA | NM_006172.4 | c.450+20G>A | intron_variant | ENST00000376480.7 | NP_006163.1 | |||
NPPA-AS1 | NR_037806.1 | n.1480-341C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NPPA | ENST00000376480.7 | c.450+20G>A | intron_variant | 1 | NM_006172.4 | ENSP00000365663 | P1 | |||
CLCN6 | ENST00000446542.5 | n.782-341C>T | intron_variant, non_coding_transcript_variant | 1 | ||||||
NPPA | ENST00000376476.1 | c.300+20G>A | intron_variant | 3 | ENSP00000365659 | |||||
CLCN6 | ENST00000400892.3 | c.*1962-484C>T | intron_variant, NMD_transcript_variant | 3 | ENSP00000496938 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152172Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000113 AC: 2AN: 176602Hom.: 0 AF XY: 0.0000107 AC XY: 1AN XY: 93412
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GnomAD4 exome AF: 0.00000366 AC: 5AN: 1364752Hom.: 0 Cov.: 31 AF XY: 0.00000299 AC XY: 2AN XY: 668652
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152172Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74336
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Atrial fibrillation, familial, 6 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 11, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
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Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at