rs5064

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006172.4(NPPA):c.123+16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.092 in 1,614,006 control chromosomes in the GnomAD database, including 8,829 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 2084 hom., cov: 32)

Exomes 𝑓: 0.088 ( 6745 hom. )

Consequence

NPPA
NM_006172.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.517

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:

ENSG00000275915 (HGNC:):

ENSG00000275915 links:

NPPA-AS1 (HGNC:37635): (NPPA antisense RNA 1)

NPPA-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 1-11847546-G-A is Benign according to our data. Variant chr1-11847546-G-A is described in ClinVar as [Benign]. Clinvar id is 36663.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-11847546-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPPA	NM_006172.4 link	c.123+16C>T		intron_variant	Intron 1 of 2	ENST00000376480.7	NP_006163.1	P01160
NPPA-AS1	NR_037806.1 link	n.1592G>A		non_coding_transcript_exon_variant	Exon 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPPA	ENST00000376480.7 link	c.123+16C>T		intron_variant	Intron 1 of 2	1	NM_006172.4	ENSP00000365663.3		P01160

Frequencies

GnomAD3 genomes

AF:

0.135

AC:

20525

AN:

152070

Hom.:

2084

Cov.:

show subpopulations

Gnomad AFR

AF:

0.284

Gnomad AMI

AF:

0.0987

Gnomad AMR

AF:

0.0895

Gnomad ASJ

AF:

0.0518

Gnomad EAS

AF:

0.00675

Gnomad SAS

AF:

0.0960

Gnomad FIN

AF:

0.0405

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.0863

Gnomad OTH

AF:

0.136

GnomAD2 exomes

AF:

0.0857

AC:

21539

AN:

251394

AF XY:

0.0840

show subpopulations

Gnomad AFR exome

AF:

0.290

Gnomad AMR exome

AF:

0.0586

Gnomad ASJ exome

AF:

0.0605

Gnomad EAS exome

AF:

0.00772

Gnomad FIN exome

AF:

0.0437

Gnomad NFE exome

AF:

0.0808

Gnomad OTH exome

AF:

0.0875

GnomAD4 exome

AF:

0.0875

AC:

127941

AN:

1461818

Hom.:

6745

Cov.:

AF XY:

0.0883

AC XY:

64213

AN XY:

727202

show subpopulations

African (AFR)

AF:

0.292

AC:

9764

AN:

33476

American (AMR)

AF:

0.0615

AC:

2749

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0617

AC:

1613

AN:

26136

East Asian (EAS)

AF:

0.00461

AC:

183

AN:

39700

South Asian (SAS)

AF:

0.110

AC:

9476

AN:

86252

European-Finnish (FIN)

AF:

0.0428

AC:

2285

AN:

53412

Middle Eastern (MID)

AF:

0.135

AC:

776

AN:

5768

European-Non Finnish (NFE)

AF:

0.0859

AC:

95490

AN:

1111954

Other (OTH)

AF:

0.0928

AC:

5605

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

7404

14807

22211

29614

37018

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.135

AC:

20534

AN:

152188

Hom.:

2084

Cov.:

AF XY:

0.132

AC XY:

9826

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.284

AC:

11769

AN:

41466

American (AMR)

AF:

0.0893

AC:

1367

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0518

AC:

180

AN:

3472

East Asian (EAS)

AF:

0.00677

AC:

AN:

5172

South Asian (SAS)

AF:

0.0959

AC:

463

AN:

4828

European-Finnish (FIN)

AF:

0.0405

AC:

430

AN:

10610

Middle Eastern (MID)

AF:

0.160

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0863

AC:

5868

AN:

68018

Other (OTH)

AF:

0.135

AC:

285

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

830

1660

2490

3320

4150

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.130

Hom.:

412

Bravo

AF:

0.145

Asia WGS

AF:

0.0540

AC:

187

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 23, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Atrial fibrillation, familial, 6

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cardiac arrhythmia

Benign:1

Aug 18, 2011

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.9

(source)

DANN

Benign

0.75

PhyloP100

-0.52

PromoterAI

-0.021

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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rs5064

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over