chr1-11845938-C-A

Position:

• chr1-11845938-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006172.4(NPPA):​c.*71G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0536 in 1,491,420 control chromosomes in the GnomAD database, including 2,420 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.041 (181 hom., cov: 32)
  • Exomes 𝑓: 0.055 (2239 hom.)
• Consequence: NPPA NM_006172.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.298

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 1-11845938-C-A is Benign according to our data. Variant chr1-11845938-C-A is described in ClinVar as [Benign]. Clinvar id is 1223314.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.*71G>T		3_prime_UTR_variant	3/3	ENST00000376480.7
NPPA-AS1	NR_037806.1	n.1479+172C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPPA	ENST00000376480.7	c.*71G>T		3_prime_UTR_variant	3/3	1	NM_006172.4	P1
CLCN6	ENST00000446542.5	n.781+172C>A		intron_variant, non_coding_transcript_variant		1
NPPA	ENST00000376476.1	c.*71G>T		3_prime_UTR_variant	3/3	3
CLCN6	ENST00000400892.3	c.*1961+172C>A		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0410 AC: 6245 AN: 152132 Hom.: 179 Cov.: 32

Gnomad AFR AF: 0.0118

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0411

Gnomad ASJ AF: 0.0683

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0479

Gnomad FIN AF: 0.0322

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0610

Gnomad OTH AF: 0.0436

GnomAD4 exome AF: 0.0550 AC: 73720 AN: 1339170 Hom.: 2239 Cov.: 21 AF XY: 0.0551 AC XY: 37066 AN XY: 673230

Gnomad4 AFR exome AF: 0.0105

Gnomad4 AMR exome AF: 0.0289

Gnomad4 ASJ exome AF: 0.0594

Gnomad4 EAS exome AF: 0.00480

Gnomad4 SAS exome AF: 0.0437

Gnomad4 FIN exome AF: 0.0336

Gnomad4 NFE exome AF: 0.0616

Gnomad4 OTH exome AF: 0.0491

GnomAD4 genome AF: 0.0410 AC: 6248 AN: 152250 Hom.: 181 Cov.: 32 AF XY: 0.0407 AC XY: 3030 AN XY: 74442

Gnomad4 AFR AF: 0.0117

Gnomad4 AMR AF: 0.0410

Gnomad4 ASJ AF: 0.0683

Gnomad4 EAS AF: 0.00231

Gnomad4 SAS AF: 0.0475

Gnomad4 FIN AF: 0.0322

Gnomad4 NFE AF: 0.0610

Gnomad4 OTH AF: 0.0470

Alfa AF: 0.0482 Hom.: 46

Bravo AF: 0.0401

Asia WGS AF: 0.0350 AC: 121 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

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.7
DANN	Benign	0.56

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

Publications

LitVar

Other links and lift over

dbSNP: rs5066; hg19: chr1-11905995;