1-11846911-GC-G

Variant names:

• chr1-11846911-GC-G
• rs67372226
• NM_006172.4:c.450+201delG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_006172.4(NPPA):​c.450+201delG 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 NM_006172.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.174
• Publications: 0 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)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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.450+201delG		intron	N/A	NP_006163.1	P01160
	NPPA-AS1	NR_037806.1		n.1480-513delC		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPPA	ENST00000376480.7	TSL:1 MANE Select	c.450+201delG		intron	N/A	ENSP00000365663.3	P01160
	CLCN6	ENST00000446542.5	TSL:1	n.782-522delC		intron	N/A
	NPPA	ENST00000376476.1	TSL:3	c.300+201delG		intron	N/A	ENSP00000365659.1	B0ZBE8

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

African (AFR) AF: 0.340 AC: 13165 AN: 38768

American (AMR) AF: 0.220 AC: 3039 AN: 13828

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 927 AN: 3338

East Asian (EAS) AF: 0.127 AC: 509 AN: 4012

South Asian (SAS) AF: 0.335 AC: 1412 AN: 4220

European-Finnish (FIN) AF: 0.278 AC: 2090 AN: 7524

Middle Eastern (MID) AF: 0.376 AC: 106 AN: 282

European-Non Finnish (NFE) AF: 0.289 AC: 18518 AN: 64114

Other (OTH) AF: 0.311 AC: 604 AN: 1944

Alfa AF: 0.130 Hom.: 179

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.17
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: rs67372226; hg19: chr1-11906968;