Variant 10-70255663-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_022146.5(NPFFR1):c.587G>T(p.Arg196Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00185 in 1,598,312 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0080 ( 16 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 25 hom. )

Consequence

NPFFR1
NM_022146.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.56

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 made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004037231).

BP6

Variant 10-70255663-C-A is Benign according to our data. Variant chr10-70255663-C-A is described in ClinVar as [Benign]. Clinvar id is 720316.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00803 (1223/152278) while in subpopulation AFR AF= 0.0275 (1143/41562). AF 95% confidence interval is 0.0262. There are 16 homozygotes in gnomad4. There are 570 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 16 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPFFR1	NM_022146.5 linkuse as main transcript	c.587G>T	p.Arg196Leu	missense_variant	4/4	ENST00000277942.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPFFR1	ENST00000277942.7 linkuse as main transcript	c.587G>T	p.Arg196Leu	missense_variant	4/4	5	NM_022146.5	P1

Frequencies

GnomAD3 genomes

AF:

0.00802

AC:

1221

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0275

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00262

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.00217

AC:

473

AN:

217896

Hom.:

AF XY:

0.00152

AC XY:

180

AN XY:

118532

show subpopulations

Gnomad AFR exome

AF:

0.0299

Gnomad AMR exome

AF:

0.00129

Gnomad ASJ exome

AF:

0.000210

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000146

Gnomad FIN exome

AF:

0.000163

Gnomad NFE exome

AF:

0.000404

Gnomad OTH exome

AF:

0.00129

GnomAD4 exome

AF:

0.00120

AC:

1739

AN:

1446034

Hom.:

Cov.:

AF XY:

0.00104

AC XY:

750

AN XY:

717706

show subpopulations

Gnomad4 AFR exome

AF:

0.0334

Gnomad4 AMR exome

AF:

0.00165

Gnomad4 ASJ exome

AF:

0.000349

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000240

Gnomad4 FIN exome

AF:

0.000174

Gnomad4 NFE exome

AF:

0.000337

Gnomad4 OTH exome

AF:

0.00207

GnomAD4 genome

AF:

0.00803

AC:

1223

AN:

152278

Hom.:

Cov.:

AF XY:

0.00766

AC XY:

570

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0275

Gnomad4 AMR

AF:

0.00262

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.00134

Hom.:

Bravo

AF:

0.00907

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0229

AC:

100

ESP6500EA

AF:

0.000469

AC:

ExAC

AF:

0.00222

AC:

268

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Mar 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.58

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.098

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.027

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.75

MetaRNN

Benign

0.0040

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.17

MutationTaster

Benign

0.76

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.11

Sift

Benign

0.080

Sift4G

Benign

0.32

Polyphen

0.17

Vest4

0.16

MVP

0.64

MPC

1.2

ClinPred

0.025

GERP RS

4.3

Varity_R

0.17

gMVP

0.61

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over