rs5066

Variant names:

• chr1-11845938-C-A
• rs5066
• NM_006172.4:c.*71G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006172.4(NPPA):​c.*71G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0536 in 1,491,420 control chromosomes in the GnomAD database, including 2,420 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.041 (181 hom., cov: 32)
  • Exomes 𝑓: 0.055 (2239 hom.)
• Consequence: NPPA NM_006172.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.298
• Publications: 15 publications found

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:37635): (NPPA antisense RNA 1)

ENSG00000278852 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 1-11845938-C-A is Benign according to our data. Variant chr1-11845938-C-A is described in ClinVar as Benign. ClinVar VariationId is 1223314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0594 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006172.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPPA	NM_006172.4	MANE Select	c.*71G>T		3_prime_UTR	Exon 3 of 3	NP_006163.1	P01160
	NPPA-AS1	NR_037806.1		n.1479+172C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPPA	ENST00000376480.7	TSL:1 MANE Select	c.*71G>T		3_prime_UTR	Exon 3 of 3	ENSP00000365663.3	P01160
	CLCN6	ENST00000446542.5	TSL:1	n.781+172C>A		intron	N/A
	NPPA	ENST00000376476.1	TSL:3	c.*71G>T		3_prime_UTR	Exon 3 of 3	ENSP00000365659.1	B0ZBE8

Frequencies

GnomAD3 genomes AF: 0.0410 AC: 6245 AN: 152132 Hom.: 179 Cov.: 32

Gnomad AFR AF: 0.0118

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0411

Gnomad ASJ AF: 0.0683

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0479

Gnomad FIN AF: 0.0322

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0610

Gnomad OTH AF: 0.0436

GnomAD4 exome AF: 0.0550 AC: 73720 AN: 1339170 Hom.: 2239 Cov.: 21 AF XY: 0.0551 AC XY: 37066 AN XY: 673230

African (AFR) AF: 0.0105 AC: 324 AN: 30812

American (AMR) AF: 0.0289 AC: 1289 AN: 44562

Ashkenazi Jewish (ASJ) AF: 0.0594 AC: 1506 AN: 25352

East Asian (EAS) AF: 0.00480 AC: 188 AN: 39132

South Asian (SAS) AF: 0.0437 AC: 3669 AN: 84032

European-Finnish (FIN) AF: 0.0336 AC: 1793 AN: 53360

Middle Eastern (MID) AF: 0.111 AC: 611 AN: 5528

European-Non Finnish (NFE) AF: 0.0616 AC: 61571 AN: 1000036

Other (OTH) AF: 0.0491 AC: 2769 AN: 56356

GnomAD4 genome AF: 0.0410 AC: 6248 AN: 152250 Hom.: 181 Cov.: 32 AF XY: 0.0407 AC XY: 3030 AN XY: 74442

African (AFR) AF: 0.0117 AC: 487 AN: 41550

American (AMR) AF: 0.0410 AC: 627 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0683 AC: 237 AN: 3472

East Asian (EAS) AF: 0.00231 AC: 12 AN: 5186

South Asian (SAS) AF: 0.0475 AC: 229 AN: 4822

European-Finnish (FIN) AF: 0.0322 AC: 341 AN: 10600

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0610 AC: 4148 AN: 68006

Other (OTH) AF: 0.0470 AC: 99 AN: 2108

Alfa AF: 0.0479 Hom.: 46

Bravo AF: 0.0401

Asia WGS AF: 0.0350 AC: 121 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.7
DANN	Benign	0.56
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs5066; hg19: chr1-11905995;