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. Variant got -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

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 Likely_benign. Variant got -4 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPPA	NM_006172.4	c.451-306_451-305dupAA		intron_variant	Intron 2 of 2	ENST00000376480.7	NP_006163.1
NPPA-AS1	NR_037806.1	n.1479+570_1479+571dupTT		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_451-304insAA		intron_variant	Intron 2 of 2	1	NM_006172.4	ENSP00000365663.3
CLCN6	ENST00000446542.5	n.781+552_781+553insTT		intron_variant	Intron 3 of 3	1
NPPA	ENST00000376476.1	c.301-305_301-304insAA		intron_variant	Intron 2 of 2	3		ENSP00000365659.1
CLCN6	ENST00000400892.3	n.*1961+552_*1961+553insTT		intron_variant	Intron 26 of 26	3		ENSP00000496938.1

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

Gnomad4 AFR AF: 0.00632

Gnomad4 AMR AF: 0.00220

Gnomad4 ASJ AF: 0.00383

Gnomad4 EAS AF: 0.00109

Gnomad4 SAS AF: 0.000532

Gnomad4 FIN AF: 0.000168

Gnomad4 NFE AF: 0.00219

Gnomad4 OTH AF: 0.00491

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;