rs5068

chr1-11845917-A-Gchr1-11845917-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006172.4(NPPA):c.*92T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0497 in 1,253,368 control chromosomes in the GnomAD database, including 1,814 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.045 (196 hom., cov: 32)
  • Exomes 𝑓: 0.050 (1618 hom.)
• Consequence: NPPA NM_006172.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.517

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 1-11845917-A-G is Benign according to our data. Variant chr1-11845917-A-G is described in ClinVar as [Benign]. Clinvar id is 1296345.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPPA	NM_006172.4	c.*92T>C		3_prime_UTR_variant	3/3	ENST00000376480.7
NPPA-AS1	NR_037806.1	n.1479+151A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPPA	ENST00000376480.7	c.*92T>C		3_prime_UTR_variant	3/3	1	NM_006172.4	P1
CLCN6	ENST00000446542.5	n.781+151A>G		intron_variant, non_coding_transcript_variant		1
NPPA	ENST00000376476.1	c.*92T>C		3_prime_UTR_variant	3/3	3
CLCN6	ENST00000400892.3	c.*1961+151A>G		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0453 AC: 6892 AN: 152162 Hom.: 196 Cov.: 32

Gnomad AFR AF: 0.0312

Gnomad AMI AF: 0.0330

Gnomad AMR AF: 0.0205

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0426

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0553

Gnomad OTH AF: 0.0306

GnomAD4 exome AF: 0.0503 AC: 55414 AN: 1101088 Hom.: 1618 Cov.: 15 AF XY: 0.0501 AC XY: 28272 AN XY: 564866

Gnomad4 AFR exome AF: 0.0318

Gnomad4 AMR exome AF: 0.0179

Gnomad4 ASJ exome AF: 0.0129

Gnomad4 EAS exome AF: 0.0000788

Gnomad4 SAS exome AF: 0.0450

Gnomad4 FIN exome AF: 0.0932

Gnomad4 NFE exome AF: 0.0545

Gnomad4 OTH exome AF: 0.0444

GnomAD4 genome AF: 0.0453 AC: 6896 AN: 152280 Hom.: 196 Cov.: 32 AF XY: 0.0470 AC XY: 3498 AN XY: 74448

Gnomad4 AFR AF: 0.0313

Gnomad4 AMR AF: 0.0205

Gnomad4 ASJ AF: 0.0115

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.0422

Gnomad4 FIN AF: 0.111

Gnomad4 NFE AF: 0.0553

Gnomad4 OTH AF: 0.0302

Alfa AF: 0.0450 Hom.: 214

Bravo AF: 0.0377

Asia WGS AF: 0.0160 AC: 56 AN: 3478

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 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	4.2
Dann	Benign	0.73

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: rs5068; hg19: chr1-11905974; COSMIC: COSV56740650; COSMIC: COSV56740650;