dbSNP rs10999212: NPFFR1:p.Pro199Pro (chr10-70255653-C-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_022146.5(NPFFR1):c.597G>T(p.Pro199Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 1,593,294 control chromosomes in the GnomAD database, including 55,464 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 0.21 ( 4289 hom., cov: 32)

Exomes 𝑓: 0.26 ( 51175 hom. )

Consequence

NPFFR1
NM_022146.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.43

Publications

10 publications found

Variant links:

Genes affected

NPFFR1 (HGNC:17425): (neuropeptide FF receptor 1) Predicted to enable G protein-coupled receptor activity and peptide binding activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Located in cilium. [provided by Alliance of Genome Resources, Apr 2022]

NPFFR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP7

Synonymous conserved (PhyloP=-1.43 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPFFR1	NM_022146.5 link	c.597G>T	p.Pro199Pro	synonymous_variant	Exon 4 of 4	ENST00000277942.7	NP_071429.1	Q9GZQ6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPFFR1	ENST00000277942.7 link	c.597G>T	p.Pro199Pro	synonymous_variant	Exon 4 of 4	5	NM_022146.5	ENSP00000277942.5		Q9GZQ6

Frequencies

GnomAD3 genomes

AF:

0.213

AC:

32356

AN:

151992

Hom.:

4288

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0946

Gnomad AMI

AF:

0.247

Gnomad AMR

AF:

0.181

Gnomad ASJ

AF:

0.183

Gnomad EAS

AF:

0.00424

Gnomad SAS

AF:

0.266

Gnomad FIN

AF:

0.378

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.280

Gnomad OTH

AF:

0.218

GnomAD2 exomes

AF:

0.221

AC:

46916

AN:

212232

AF XY:

0.227

show subpopulations

Gnomad AFR exome

AF:

0.0872

Gnomad AMR exome

AF:

0.142

Gnomad ASJ exome

AF:

0.181

Gnomad EAS exome

AF:

0.00417

Gnomad FIN exome

AF:

0.363

Gnomad NFE exome

AF:

0.268

Gnomad OTH exome

AF:

0.227

GnomAD4 exome

AF:

0.259

AC:

372834

AN:

1441184

Hom.:

51175

Cov.:

AF XY:

0.259

AC XY:

185003

AN XY:

714748

show subpopulations

African (AFR)

AF:

0.0858

AC:

2843

AN:

33122

American (AMR)

AF:

0.154

AC:

6412

AN:

41754

Ashkenazi Jewish (ASJ)

AF:

0.181

AC:

4662

AN:

25754

East Asian (EAS)

AF:

0.00249

AC:

AN:

38908

South Asian (SAS)

AF:

0.266

AC:

22034

AN:

82944

European-Finnish (FIN)

AF:

0.367

AC:

18804

AN:

51260

Middle Eastern (MID)

AF:

0.205

AC:

1180

AN:

5750

European-Non Finnish (NFE)

AF:

0.274

AC:

302495

AN:

1102076

Other (OTH)

AF:

0.240

AC:

14307

AN:

59616

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

18019

36038

54056

72075

90094

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9886

19772

29658

39544

49430

<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:

0.213

AC:

32357

AN:

152110

Hom.:

4289

Cov.:

AF XY:

0.218

AC XY:

16173

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.0945

AC:

3925

AN:

41534

American (AMR)

AF:

0.181

AC:

2772

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.183

AC:

635

AN:

3470

East Asian (EAS)

AF:

0.00425

AC:

AN:

5180

South Asian (SAS)

AF:

0.267

AC:

1287

AN:

4824

European-Finnish (FIN)

AF:

0.378

AC:

3999

AN:

10566

Middle Eastern (MID)

AF:

0.180

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.279

AC:

18984

AN:

67930

Other (OTH)

AF:

0.216

AC:

455

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1220

2440

3660

4880

6100

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

340

680

1020

1360

1700

<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:

0.241

Hom.:

5444

Bravo

AF:

0.190

Asia WGS

AF:

0.133

AC:

463

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

4.9

(source)

DANN

Benign

0.91

PhyloP100

-1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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