dbSNP rs8192593: NPFF:n.164C>T (chr12-53507321-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The ENST00000448979.4(NPFF):n.164C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0318 in 1,611,386 control chromosomes in the GnomAD database, including 939 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.022 ( 51 hom., cov: 32)

Exomes 𝑓: 0.033 ( 888 hom. )

Consequence

NPFF
ENST00000448979.4 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.325

Publications

5 publications found

Variant links:

Genes affected

NPFF (HGNC:7901): (neuropeptide FF-amide peptide precursor) This gene encodes a member of the FMRFamide related peptide (FARP) family of neuropeptides. The encoded preproprotein is proteolytically processed to generate multiple amidated peptides. These peptides may play a role in the regulation of heart rate and blood pressure and the modulation of morphine-induced antinociception. Patients with hypertension exhibit decreased expression of the encoded protein. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Feb 2016]

NPFF links:

ATF7-NPFF (HGNC:55073): (ATF7-NPFF readthrough) Predicted to enable DNA binding activity and DNA-binding transcription factor activity. Predicted to be involved in regulation of transcription, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ATF7-NPFF links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0222 (3386/152256) while in subpopulation NFE AF = 0.0361 (2455/68000). AF 95% confidence interval is 0.0349. There are 51 homozygotes in GnomAd4. There are 1575 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 51 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPFF	NM_003717.4 link	c.102+52C>T		intron_variant	Intron 1 of 2	ENST00000267017.4	NP_003708.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
NPFF	ENST00000448979.4 link	n.164C>T	non_coding_transcript_exon_variant	Exon 1 of 2	1
NPFF	ENST00000267017.4 link	c.102+52C>T	intron_variant	Intron 1 of 2	1	NM_003717.4	ENSP00000267017.3
ATF7-NPFF	ENST00000591834.1 link	c.1235-179C>T	intron_variant	Intron 11 of 12	5		ENSP00000466174.1

Frequencies

GnomAD3 genomes

AF:

0.0223

AC:

3386

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00722

Gnomad AMI

AF:

0.0439

Gnomad AMR

AF:

0.0158

Gnomad ASJ

AF:

0.00835

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00829

Gnomad FIN

AF:

0.0230

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0361

Gnomad OTH

AF:

0.0173

GnomAD4 exome

AF:

0.0328

AC:

47830

AN:

1459130

Hom.:

888

Cov.:

AF XY:

0.0318

AC XY:

23049

AN XY:

725380

show subpopulations

African (AFR)

AF:

0.00502

AC:

168

AN:

33442

American (AMR)

AF:

0.0123

AC:

547

AN:

44646

Ashkenazi Jewish (ASJ)

AF:

0.0109

AC:

283

AN:

26040

East Asian (EAS)

AF:

0.000101

AC:

AN:

39606

South Asian (SAS)

AF:

0.00782

AC:

674

AN:

86196

European-Finnish (FIN)

AF:

0.0255

AC:

1358

AN:

53152

Middle Eastern (MID)

AF:

0.00330

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0388

AC:

43043

AN:

1109998

Other (OTH)

AF:

0.0288

AC:

1734

AN:

60286

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

2346

4692

7039

9385

11731

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1612

3224

4836

6448

8060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0222

AC:

3386

AN:

152256

Hom.:

Cov.:

AF XY:

0.0212

AC XY:

1575

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.00720

AC:

299

AN:

41548

American (AMR)

AF:

0.0158

AC:

242

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00835

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5184

South Asian (SAS)

AF:

0.00830

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0230

AC:

244

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0361

AC:

2455

AN:

68000

Other (OTH)

AF:

0.0171

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

174

349

523

698

872

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

168

210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0314

Hom.:

234

Bravo

AF:

0.0206

Asia WGS

AF:

0.00346

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

2.9

(source)

DANN

Benign

0.59

PhyloP100

0.33

PromoterAI

-0.046

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=300/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over