1-11846318-C-CT

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_006172.4(NPPA):c.451-305_451-304insA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.19 (3747 hom., cov: 24)
  • Failed GnomAD Quality Control
• Consequence: NPPA NM_006172.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.497

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]

NPPA-AS1 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 1-11846318-C-CT is Benign according to our data. Variant chr1-11846318-C-CT is described in ClinVar as [Benign]. Clinvar id is 1282231.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPPA	NM_006172.4	c.451-305_451-304insA		intron_variant		ENST00000376480.7
NPPA-AS1	NR_037806.1	n.1479+571dup		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPPA	ENST00000376480.7	c.451-305_451-304insA		intron_variant		1	NM_006172.4	P1
CLCN6	ENST00000446542.5	n.781+571dup		intron_variant, non_coding_transcript_variant		1
NPPA	ENST00000376476.1	c.301-305_301-304insA		intron_variant		3
CLCN6	ENST00000400892.3	c.*1961+571dup		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 23379 AN: 121318 Hom.: 3747 Cov.: 24 FAILED QC

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.0296

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.0383

Gnomad MID AF: 0.202

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.194

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.193 AC: 23379 AN: 121310 Hom.: 3747 Cov.: 24 AF XY: 0.187 AC XY: 10834 AN XY: 57852

Gnomad4 AFR AF: 0.379

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.0290

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.0383

Gnomad4 NFE AF: 0.152

Gnomad4 OTH AF: 0.193

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs71568361; hg19: chr1-11906375;