1-11846318-CTTTTTTTTTT-CTTTTTTTTTTTTTTT

Variant names:

• chr1-11846318-C-CTTTTT
• rs71568361
• NM_006172.4:c.451-309_451-305dupAAAAA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006172.4(NPPA):​c.451-309_451-305dupAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000412 in 121,330 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000041 (0 hom., cov: 24)
• Consequence: NPPA NM_006172.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.497

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPPA	NM_006172.4	c.451-309_451-305dupAAAAA		intron_variant	Intron 2 of 2	ENST00000376480.7	NP_006163.1
NPPA-AS1	NR_037806.1	n.1479+567_1479+571dupTTTTT		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPPA	ENST00000376480.7	c.451-305_451-304insAAAAA		intron_variant	Intron 2 of 2	1	NM_006172.4	ENSP00000365663.3
CLCN6	ENST00000446542.5	n.781+552_781+553insTTTTT		intron_variant	Intron 3 of 3	1
NPPA	ENST00000376476.1	c.301-305_301-304insAAAAA		intron_variant	Intron 2 of 2	3		ENSP00000365659.1
CLCN6	ENST00000400892.3	n.*1961+552_*1961+553insTTTTT		intron_variant	Intron 26 of 26	3		ENSP00000496938.1

Frequencies

GnomAD3 genomes AF: 0.0000412 AC: 5 AN: 121338 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.000133

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000168

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000412 AC: 5 AN: 121330 Hom.: 0 Cov.: 24 AF XY: 0.0000346 AC XY: 2 AN XY: 57862

Gnomad4 AFR AF: 0.000133

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000169

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs71568361; hg19: chr1-11906375;