1-11846318-CTTTTTTTTTT-CTTTTTTTTTTTT

Variant names:

• chr1-11846318-C-CTT
• rs71568361
• NM_006172.4:c.451-306_451-305dupAA

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_006172.4(NPPA):​c.451-306_451-305dupAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00309 in 121,326 control chromosomes in the GnomAD database, including 5 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0031 (5 hom., cov: 24)
• Consequence: NPPA NM_006172.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.497
• 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 5 AD,Unknown,AR gene

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.451-306_451-305dupAA		intron	N/A	NP_006163.1	P01160
	NPPA-AS1	NR_037806.1		n.1479+570_1479+571dupTT		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPPA	ENST00000376480.7	TSL:1 MANE Select	c.451-305_451-304insAA		intron	N/A	ENSP00000365663.3	P01160
	CLCN6	ENST00000446542.5	TSL:1	n.781+552_781+553insTT		intron	N/A
	NPPA	ENST00000376476.1	TSL:3	c.301-305_301-304insAA		intron	N/A	ENSP00000365659.1	B0ZBE8

Frequencies

GnomAD3 genomes AF: 0.00304 AC: 369 AN: 121334 Hom.: 5 Cov.: 24

Gnomad AFR AF: 0.00626

Gnomad AMI AF: 0.00122

Gnomad AMR AF: 0.00220

Gnomad ASJ AF: 0.00383

Gnomad EAS AF: 0.00109

Gnomad SAS AF: 0.000530

Gnomad FIN AF: 0.000168

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00219

Gnomad OTH AF: 0.00246

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

GnomAD4 genome AF: 0.00309 AC: 375 AN: 121326 Hom.: 5 Cov.: 24 AF XY: 0.00332 AC XY: 192 AN XY: 57854

African (AFR) AF: 0.00632 AC: 190 AN: 30054

American (AMR) AF: 0.00220 AC: 26 AN: 11820

Ashkenazi Jewish (ASJ) AF: 0.00383 AC: 12 AN: 3134

East Asian (EAS) AF: 0.00109 AC: 5 AN: 4588

South Asian (SAS) AF: 0.000532 AC: 2 AN: 3756

European-Finnish (FIN) AF: 0.000168 AC: 1 AN: 5948

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.00219 AC: 130 AN: 59342

Other (OTH) AF: 0.00491 AC: 8 AN: 1628

Alfa AF: 0.000711 Hom.: 48

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.50
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs71568361; hg19: chr1-11906375;