1-11846921-C-CT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_006172.4(NPPA):c.450+191_450+192insA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 125,020 control chromosomes in the GnomAD database, including 1,459 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.15 (1459 hom., cov: 24)
• Consequence: NPPA NM_006172.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.08

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 Benign. Variant got -10 ACMG points.

• BP6: Variant 1-11846921-C-CT is Benign according to our data. Variant chr1-11846921-C-CT is described in ClinVar as [Benign]. Clinvar id is 1226929.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPPA	NM_006172.4	c.450+191_450+192insA		intron_variant		ENST00000376480.7
NPPA-AS1	NR_037806.1	n.1480-503dup		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPPA	ENST00000376480.7	c.450+191_450+192insA		intron_variant		1	NM_006172.4	P1
CLCN6	ENST00000446542.5	n.782-503dup		intron_variant, non_coding_transcript_variant		1
NPPA	ENST00000376476.1	c.300+191_300+192insA		intron_variant		3
CLCN6	ENST00000400892.3	c.*1962-646dup		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.148 AC: 18498 AN: 124942 Hom.: 1456 Cov.: 24

Gnomad AFR AF: 0.0369

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.0781

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.150

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

GnomAD4 genome AF: 0.148 AC: 18503 AN: 125020 Hom.: 1459 Cov.: 24 AF XY: 0.150 AC XY: 9006 AN XY: 59892

Gnomad4 AFR AF: 0.0368

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.408

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.249

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.150

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

Mar 01, 2019

- -

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: rs1553122981; hg19: chr1-11906978;