rs67372226

Variant names:

• chr1-11846911-GCC-G
• rs67372226
• NM_006172.4:c.450+200_450+201delGG

Your query was ambiguous. Multiple possible variants found:

• chr1-11846911-GCC-G
• chr1-11846911-GCC-GC
• chr1-11846911-GCC-GCCC
• chr1-11846911-GCC-GCCCC
• chr1-11846911-GCC-GCCCCC
• chr1-11846911-GCC-GCCCCCC
• chr1-11846911-GCC-GCCCCCCC

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+200_450+201delGG variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.067 (356 hom., cov: 0)
• Consequence: NPPA NM_006172.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.667
• 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-GCC-G is Benign according to our data. Variant chr1-11846911-GCC-G is described in ClinVar as Benign. ClinVar VariationId is 1296379.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0913 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+200_450+201delGG		intron	N/A	NP_006163.1	P01160
	NPPA-AS1	NR_037806.1		n.1480-514_1480-513delCC		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+200_450+201delGG		intron	N/A	ENSP00000365663.3	P01160
	CLCN6	ENST00000446542.5	TSL:1	n.782-522_782-521delCC		intron	N/A
	NPPA	ENST00000376476.1	TSL:3	c.300+200_300+201delGG		intron	N/A	ENSP00000365659.1	B0ZBE8

Frequencies

GnomAD3 genomes AF: 0.0673 AC: 9344 AN: 138924 Hom.: 353 Cov.: 0

Gnomad AFR AF: 0.0938

Gnomad AMI AF: 0.0539

Gnomad AMR AF: 0.0513

Gnomad ASJ AF: 0.0566

Gnomad EAS AF: 0.00372

Gnomad SAS AF: 0.0517

Gnomad FIN AF: 0.0394

Gnomad MID AF: 0.0806

Gnomad NFE AF: 0.0639

Gnomad OTH AF: 0.0606

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

GnomAD4 genome AF: 0.0673 AC: 9356 AN: 138968 Hom.: 356 Cov.: 0 AF XY: 0.0674 AC XY: 4508 AN XY: 66846

African (AFR) AF: 0.0938 AC: 3639 AN: 38790

American (AMR) AF: 0.0512 AC: 708 AN: 13828

Ashkenazi Jewish (ASJ) AF: 0.0566 AC: 189 AN: 3340

East Asian (EAS) AF: 0.00373 AC: 15 AN: 4018

South Asian (SAS) AF: 0.0514 AC: 217 AN: 4224

European-Finnish (FIN) AF: 0.0394 AC: 297 AN: 7536

Middle Eastern (MID) AF: 0.0816 AC: 23 AN: 282

European-Non Finnish (NFE) AF: 0.0639 AC: 4097 AN: 64150

Other (OTH) AF: 0.0642 AC: 125 AN: 1946

Alfa AF: 0.0137 Hom.: 179

ClinVar

ClinVar submissions as Germline

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		0.67
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; COSMIC: COSV56740172; COSMIC: COSV56740172;