chr1-11846911-GC-G

Position:

• chr1-11846911-GC-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000376480.7(NPPA):​c.450+201del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.29 (5874 hom., cov: 0)
• Consequence: NPPA ENST00000376480.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.174

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:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 1-11846911-GC-G is Benign according to our data. Variant chr1-11846911-GC-G is described in ClinVar as [Benign]. Clinvar id is 1178505.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPPA	NM_006172.4	c.450+201del		intron_variant		ENST00000376480.7	NP_006163.1
NPPA-AS1	NR_037806.1	n.1480-513del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPPA	ENST00000376480.7	c.450+201del		intron_variant		1	NM_006172.4	ENSP00000365663	P1
CLCN6	ENST00000446542.5	n.782-513del		intron_variant, non_coding_transcript_variant		1
NPPA	ENST00000376476.1	c.300+201del		intron_variant		3		ENSP00000365659
CLCN6	ENST00000400892.3	c.*1962-656del		intron_variant, NMD_transcript_variant		3		ENSP00000496938

Frequencies

GnomAD3 genomes AF: 0.293 AC: 40656 AN: 138840 Hom.: 5875 Cov.: 0

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.390

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.312

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.293 AC: 40663 AN: 138884 Hom.: 5874 Cov.: 0 AF XY: 0.292 AC XY: 19503 AN XY: 66790

Gnomad4 AFR AF: 0.340

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.278

Gnomad4 EAS AF: 0.127

Gnomad4 SAS AF: 0.335

Gnomad4 FIN AF: 0.278

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.311

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 13, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs67372226; hg19: chr1-11906968;