Variant 4-72128808-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_004885.3(NPFFR2):c.217A>G(p.Asn73Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000546 in 1,614,098 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0032 ( 5 hom., cov: 30)

Exomes 𝑓: 0.00027 ( 3 hom. )

Consequence

NPFFR2
NM_004885.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.38

Variant links:

Genes affected

NPFFR2 (HGNC:4525): (neuropeptide FF receptor 2) This gene encodes a member of a subfamily of G-protein-coupled neuropeptide receptors. This protein is activated by the neuropeptides A-18-amide (NPAF) and F-8-amide (NPFF) and may function in pain modulation and regulation of the opioid system. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2009]

NPFFR2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012522399).

BP6

Variant 4-72128808-A-G is Benign according to our data. Variant chr4-72128808-A-G is described in ClinVar as [Benign]. Clinvar id is 788409.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
NPFFR2	NM_004885.3 linkuse as main transcript	c.217A>G	p.Asn73Asp	missense_variant	2/4	ENST00000308744.12
NPFFR2	NM_001144756.2 linkuse as main transcript	c.226A>G	p.Asn76Asp	missense_variant	3/5
NPFFR2	NM_053036.3 linkuse as main transcript	c.217A>G	p.Asn73Asp	missense_variant	2/4
NPFFR2	XM_011531554.3 linkuse as main transcript	c.305-9232A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPFFR2	ENST00000308744.12 linkuse as main transcript	c.217A>G	p.Asn73Asp	missense_variant	2/4	1	NM_004885.3	P4	Q9Y5X5-2
NPFFR2	ENST00000395999.5 linkuse as main transcript	c.226A>G	p.Asn76Asp	missense_variant	3/5	1		A2	Q9Y5X5-3
NPFFR2	ENST00000358749.3 linkuse as main transcript	c.217A>G	p.Asn73Asp	missense_variant	2/4	1		P4	Q9Y5X5-2
NPFFR2	ENST00000344413.6 linkuse as main transcript	c.-20-9232A>G		intron_variant		1

Frequencies

GnomAD3 genomes

AF:

0.00317

AC:

482

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0110

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.000688

AC:

173

AN:

251366

Hom.:

AF XY:

0.000559

AC XY:

AN XY:

135856

show subpopulations

Gnomad AFR exome

AF:

0.00991

Gnomad AMR exome

AF:

0.000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000273

AC:

399

AN:

1461768

Hom.:

Cov.:

AF XY:

0.000234

AC XY:

170

AN XY:

727192

show subpopulations

Gnomad4 AFR exome

AF:

0.0103

Gnomad4 AMR exome

AF:

0.000291

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.000629

GnomAD4 genome

AF:

0.00316

AC:

482

AN:

152330

Hom.:

Cov.:

AF XY:

0.00321

AC XY:

239

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0109

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000511

Hom.:

Bravo

AF:

0.00337

ESP6500AA

AF:

0.0120

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000848

AC:

103

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Labcorp Genetics (formerly Invitae), Labcorp

Jan 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.060

T;.;.

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.82

T;T;T

MetaRNN

Benign

0.013

T;T;T

MetaSVM

Uncertain

0.0034

MutationAssessor

Uncertain

2.8

M;.;.

MutationTaster

Benign

0.79

D;D;D;D

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-3.4

D;D;D

REVEL

Uncertain

0.48

Sift

Benign

0.066

T;D;D

Sift4G

Benign

0.072

T;.;T

Polyphen

0.89

P;P;.

Vest4

0.32

MVP

0.82

MPC

0.16

ClinPred

0.098

GERP RS

4.7

Varity_R

0.26

gMVP

0.25

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