NM_006172.4:c.*215T>C

Variant names:

• chr1-11845794-A-G
• rs61764044
• NM_006172.4:c.*215T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006172.4(NPPA):​c.*215T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0469 in 603,488 control chromosomes in the GnomAD database, including 844 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.045 (194 hom., cov: 32)
  • Exomes 𝑓: 0.047 (650 hom.)
• Consequence: NPPA NM_006172.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0970
• Publications: 10 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)

ENSG00000278852 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 1-11845794-A-G is Benign according to our data. Variant chr1-11845794-A-G is described in ClinVar as Benign. ClinVar VariationId is 1296344.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0536 is higher than 0.05.

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.*215T>C		3_prime_UTR	Exon 3 of 3	NP_006163.1	P01160
	NPPA-AS1	NR_037806.1		n.1479+28A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPPA	ENST00000376480.7	TSL:1 MANE Select	c.*215T>C		3_prime_UTR	Exon 3 of 3	ENSP00000365663.3	P01160
	CLCN6	ENST00000446542.5	TSL:1	n.781+28A>G		intron	N/A
	NPPA	ENST00000953330.1		c.*215T>C		3_prime_UTR	Exon 2 of 2	ENSP00000623389.1

Frequencies

GnomAD3 genomes AF: 0.0452 AC: 6878 AN: 152210 Hom.: 194 Cov.: 32

Gnomad AFR AF: 0.0311

Gnomad AMI AF: 0.0330

Gnomad AMR AF: 0.0203

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0428

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0551

Gnomad OTH AF: 0.0306

GnomAD4 exome AF: 0.0474 AC: 21400 AN: 451160 Hom.: 650 Cov.: 3 AF XY: 0.0473 AC XY: 11275 AN XY: 238254

African (AFR) AF: 0.0333 AC: 419 AN: 12592

American (AMR) AF: 0.0211 AC: 449 AN: 21252

Ashkenazi Jewish (ASJ) AF: 0.0124 AC: 173 AN: 13902

East Asian (EAS) AF: 0.0000324 AC: 1 AN: 30874

South Asian (SAS) AF: 0.0448 AC: 2033 AN: 45362

European-Finnish (FIN) AF: 0.0900 AC: 3089 AN: 34330

Middle Eastern (MID) AF: 0.0318 AC: 62 AN: 1950

European-Non Finnish (NFE) AF: 0.0531 AC: 14058 AN: 264990

Other (OTH) AF: 0.0431 AC: 1116 AN: 25908

GnomAD4 genome AF: 0.0452 AC: 6882 AN: 152328 Hom.: 194 Cov.: 32 AF XY: 0.0469 AC XY: 3493 AN XY: 74486

African (AFR) AF: 0.0312 AC: 1297 AN: 41572

American (AMR) AF: 0.0202 AC: 309 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0115 AC: 40 AN: 3472

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5188

South Asian (SAS) AF: 0.0424 AC: 205 AN: 4830

European-Finnish (FIN) AF: 0.111 AC: 1173 AN: 10614

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0551 AC: 3748 AN: 68034

Other (OTH) AF: 0.0303 AC: 64 AN: 2114

Alfa AF: 0.0492 Hom.: 46

Bravo AF: 0.0376

Asia WGS AF: 0.0160 AC: 56 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.1
DANN	Benign	0.67
PhyloP100		0.097
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
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: rs61764044; hg19: chr1-11905851; COSMIC: COSV56741536; COSMIC: COSV56741536;