rs5068

Variant names:

• chr1-11845917-A-G
• rs5068
• NM_006172.4:c.*92T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-11845917-A-G
• chr1-11845917-A-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.*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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.517
• Publications: 112 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=-0.8).
• BP6: Variant 1-11845917-A-G is Benign according to our data. Variant chr1-11845917-A-G is described in ClinVar as Benign. ClinVar VariationId is 1296345.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPPA	NM_006172.4	c.*92T>C		3_prime_UTR_variant	Exon 3 of 3	ENST00000376480.7	NP_006163.1
NPPA-AS1	NR_037806.1	n.1479+151A>G		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPPA	ENST00000376480.7	c.*92T>C		3_prime_UTR_variant	Exon 3 of 3	1	NM_006172.4	ENSP00000365663.3

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

African (AFR) AF: 0.0318 AC: 830 AN: 26138

American (AMR) AF: 0.0179 AC: 790 AN: 44240

Ashkenazi Jewish (ASJ) AF: 0.0129 AC: 308 AN: 23874

East Asian (EAS) AF: 0.0000788 AC: 3 AN: 38088

South Asian (SAS) AF: 0.0450 AC: 3566 AN: 79170

European-Finnish (FIN) AF: 0.0932 AC: 4965 AN: 53252

Middle Eastern (MID) AF: 0.0247 AC: 126 AN: 5094

European-Non Finnish (NFE) AF: 0.0545 AC: 42678 AN: 782806

Other (OTH) AF: 0.0444 AC: 2148 AN: 48426

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

African (AFR) AF: 0.0313 AC: 1299 AN: 41556

American (AMR) AF: 0.0205 AC: 313 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0115 AC: 40 AN: 3472

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5188

South Asian (SAS) AF: 0.0422 AC: 204 AN: 4830

European-Finnish (FIN) AF: 0.111 AC: 1172 AN: 10602

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0553 AC: 3758 AN: 68010

Other (OTH) AF: 0.0302 AC: 64 AN: 2116

Alfa AF: 0.0455 Hom.: 310

Bravo AF: 0.0377

Asia WGS AF: 0.0160 AC: 56 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 14, 2021

GeneDx

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	-0.80
CADD	Benign	4.2
DANN	Benign	0.73
PhyloP100		0.52
Mutation Taster		=100/0	polymorphism (auto)

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