1-11845740-TCACTTTCAAAC-T

Position:

• chr1-11845740-TCACTTTCAAAC-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_006172.4(NPPA):​c.*258_*268del variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.046 in 545,770 control chromosomes in the GnomAD database, including 710 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.041 (172 hom., cov: 32)
  • Exomes 𝑓: 0.048 (538 hom.)
• Consequence: NPPA NM_006172.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.25

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:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 1-11845740-TCACTTTCAAAC-T is Benign according to our data. Variant chr1-11845740-TCACTTTCAAAC-T is described in ClinVar as [Benign]. Clinvar id is 1276720.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPPA	NM_006172.4	c.*258_*268del		3_prime_UTR_variant	3/3	ENST00000376480.7
NPPA-AS1	NR_037806.1	n.1462_1472del		non_coding_transcript_exon_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPPA	ENST00000376480.7	c.*258_*268del		3_prime_UTR_variant	3/3	1	NM_006172.4	P1
CLCN6	ENST00000446542.5	n.764_774del		non_coding_transcript_exon_variant	3/4	1
CLCN6	ENST00000400892.3	c.*1944_*1954del		3_prime_UTR_variant, NMD_transcript_variant	26/27	3
	ENST00000618496.1			downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.0409 AC: 6227 AN: 152184 Hom.: 172 Cov.: 32

Gnomad AFR AF: 0.0116

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0405

Gnomad ASJ AF: 0.0683

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.0480

Gnomad FIN AF: 0.0325

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0609

Gnomad OTH AF: 0.0431

GnomAD4 exome AF: 0.0481 AC: 18907 AN: 393468 Hom.: 538 AF XY: 0.0486 AC XY: 10031 AN XY: 206220

Gnomad4 AFR exome AF: 0.0128

Gnomad4 AMR exome AF: 0.0343

Gnomad4 ASJ exome AF: 0.0610

Gnomad4 EAS exome AF: 0.00527

Gnomad4 SAS exome AF: 0.0419

Gnomad4 FIN exome AF: 0.0340

Gnomad4 NFE exome AF: 0.0578

Gnomad4 OTH exome AF: 0.0460

GnomAD4 genome AF: 0.0409 AC: 6222 AN: 152302 Hom.: 172 Cov.: 32 AF XY: 0.0407 AC XY: 3029 AN XY: 74474

Gnomad4 AFR AF: 0.0115

Gnomad4 AMR AF: 0.0404

Gnomad4 ASJ AF: 0.0683

Gnomad4 EAS AF: 0.00212

Gnomad4 SAS AF: 0.0476

Gnomad4 FIN AF: 0.0325

Gnomad4 NFE AF: 0.0609

Gnomad4 OTH AF: 0.0426

Alfa AF: 0.0411 Hom.: 22

Bravo AF: 0.0400

Asia WGS AF: 0.0260 AC: 92 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 20, 2020

- -

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: rs63749086; hg19: chr1-11905797;