1-11846318-CTTTTTTTTTT-CTTTTTTTTTTT

Variant names:

• chr1-11846318-C-CT
• rs71568361
• NM_006172.4:c.451-305dupA

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_006172.4(NPPA):​c.451-305dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.19 (3747 hom., cov: 24)
  • Failed GnomAD Quality Control
• Consequence: NPPA NM_006172.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -2 ACMG points.

• BP6: Variant 1-11846318-C-CT is Benign according to our data. Variant chr1-11846318-C-CT is described in ClinVar as Benign. ClinVar VariationId is 1282231.Status of the report is criteria_provided_single_submitter, 1 stars.

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.451-305dupA		intron	N/A	NP_006163.1	P01160
	NPPA-AS1	NR_037806.1		n.1479+571dupT		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_451-304insA		intron	N/A	ENSP00000365663.3	P01160
	CLCN6	ENST00000446542.5	TSL:1	n.781+552_781+553insT		intron	N/A
	NPPA	ENST00000376476.1	TSL:3	c.301-305_301-304insA		intron	N/A	ENSP00000365659.1	B0ZBE8

Frequencies

GnomAD3 genomes AF: 0.193 AC: 23379 AN: 121318 Hom.: 3747 Cov.: 24

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.0296

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.0383

Gnomad MID AF: 0.202

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.194

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

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.193 AC: 23379 AN: 121310 Hom.: 3747 Cov.: 24 AF XY: 0.187 AC XY: 10834 AN XY: 57852

African (AFR) AF: 0.379 AC: 11392 AN: 30060

American (AMR) AF: 0.108 AC: 1281 AN: 11822

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 360 AN: 3132

East Asian (EAS) AF: 0.0290 AC: 133 AN: 4588

South Asian (SAS) AF: 0.127 AC: 477 AN: 3754

European-Finnish (FIN) AF: 0.0383 AC: 228 AN: 5948

Middle Eastern (MID) AF: 0.218 AC: 52 AN: 238

European-Non Finnish (NFE) AF: 0.152 AC: 9024 AN: 59322

Other (OTH) AF: 0.193 AC: 315 AN: 1628

Alfa AF: 0.0235 Hom.: 48

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		-0.50
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: rs71568361; hg19: chr1-11906375;