Variant 1-11845794-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000376480.7(NPPA):c.*215T>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 0.0469 in 603,488 control chromosomes in the GnomAD database, including 844 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.045 ( 194 hom., cov: 32)

Exomes 𝑓: 0.047 ( 650 hom. )

Consequence

NPPA
ENST00000376480.7 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0970

Variant links:

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]

NPPA links:

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]

CLCN6 links:

NPPA-AS1 (HGNC:):

NPPA-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 1-11845794-A-G is Benign according to our data. Variant chr1-11845794-A-G is described in ClinVar as [Benign]. Clinvar id is 1296344.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPPA	NM_006172.4 linkuse as main transcript	c.*215T>C		3_prime_UTR_variant	3/3	ENST00000376480.7	NP_006163.1
NPPA-AS1	NR_037806.1 linkuse as main transcript	n.1479+28A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
NPPA	ENST00000376480.7 linkuse as main transcript	c.*215T>C	3_prime_UTR_variant	3/3	1	NM_006172.4	ENSP00000365663	P1
CLCN6	ENST00000446542.5 linkuse as main transcript	n.781+28A>G	intron_variant, non_coding_transcript_variant		1
CLCN6	ENST00000400892.3 linkuse as main transcript	c.*1961+28A>G	intron_variant, NMD_transcript_variant		3		ENSP00000496938

Frequencies

GnomAD3 genomes

AF:

0.0452

AC:

6878

AN:

152210

Hom.:

194

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0311

Gnomad AMI

AF:

0.0330

Gnomad AMR

AF:

0.0203

Gnomad ASJ

AF:

0.0115

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.0428

Gnomad FIN

AF:

0.111

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0551

Gnomad OTH

AF:

0.0306

GnomAD4 exome

AF:

0.0474

AC:

21400

AN:

451160

Hom.:

650

Cov.:

AF XY:

0.0473

AC XY:

11275

AN XY:

238254

show subpopulations

Gnomad4 AFR exome

AF:

0.0333

Gnomad4 AMR exome

AF:

0.0211

Gnomad4 ASJ exome

AF:

0.0124

Gnomad4 EAS exome

AF:

0.0000324

Gnomad4 SAS exome

AF:

0.0448

Gnomad4 FIN exome

AF:

0.0900

Gnomad4 NFE exome

AF:

0.0531

Gnomad4 OTH exome

AF:

0.0431

GnomAD4 genome

AF:

0.0452

AC:

6882

AN:

152328

Hom.:

194

Cov.:

AF XY:

0.0469

AC XY:

3493

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0312

Gnomad4 AMR

AF:

0.0202

Gnomad4 ASJ

AF:

0.0115

Gnomad4 EAS

AF:

0.000771

Gnomad4 SAS

AF:

0.0424

Gnomad4 FIN

AF:

0.111

Gnomad4 NFE

AF:

0.0551

Gnomad4 OTH

AF:

0.0303

Alfa

AF:

0.0492

Hom.:

Bravo

AF:

0.0376

Asia WGS

AF:

0.0160

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 14, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

9.1

DANN

Benign

0.67

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over