rs5067

Variant names:

• chr1-11845924-A-G
• rs5067
• NM_006172.4:c.*85T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-11845924-A-G
• chr1-11845924-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006172.4(NPPA):​c.*85T>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 0.148 in 1,338,838 control chromosomes in the GnomAD database, including 18,007 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (4477 hom., cov: 32)
  • Exomes 𝑓: 0.14 (13530 hom.)
• Consequence: NPPA NM_006172.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.638

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)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 1-11845924-A-G is Benign according to our data. Variant chr1-11845924-A-G is described in ClinVar as [Benign]. Clinvar id is 1233521.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPPA	NM_006172.4	c.*85T>C		3_prime_UTR_variant	Exon 3 of 3	ENST00000376480.7	NP_006163.1
NPPA-AS1	NR_037806.1	n.1479+158A>G		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPPA	ENST00000376480	c.*85T>C		3_prime_UTR_variant	Exon 3 of 3	1	NM_006172.4	ENSP00000365663.3
CLCN6	ENST00000446542.5	n.781+158A>G		intron_variant	Intron 3 of 3	1
NPPA	ENST00000376476	c.*85T>C		3_prime_UTR_variant	Exon 3 of 3	3		ENSP00000365659.1
CLCN6	ENST00000400892.3	n.*1961+158A>G		intron_variant	Intron 26 of 26	3		ENSP00000496938.1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31416 AN: 152046 Hom.: 4470 Cov.: 32

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.0106

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.0730

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.201

GnomAD4 exome AF: 0.141 AC: 166805 AN: 1186674 Hom.: 13530 Cov.: 16 AF XY: 0.141 AC XY: 85375 AN XY: 603886

Gnomad4 AFR exome AF: 0.404

Gnomad4 AMR exome AF: 0.0948

Gnomad4 ASJ exome AF: 0.120

Gnomad4 EAS exome AF: 0.00969

Gnomad4 SAS exome AF: 0.154

Gnomad4 FIN exome AF: 0.0761

Gnomad4 NFE exome AF: 0.143

Gnomad4 OTH exome AF: 0.147

GnomAD4 genome AF: 0.207 AC: 31446 AN: 152164 Hom.: 4477 Cov.: 32 AF XY: 0.203 AC XY: 15111 AN XY: 74396

Gnomad4 AFR AF: 0.403

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.0106

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.0730

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.203

Alfa AF: 0.182 Hom.: 1262

Bravo AF: 0.219

Asia WGS AF: 0.0990 AC: 346 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Sep 04, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.54
DANN	Benign	0.56

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: rs5067; hg19: chr1-11905981;