Variant chr4-72138099-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_004885.3(NPFFR2):c.388G>A(p.Ala130Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000369 in 1,613,646 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0019 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00021 ( 1 hom. )

Consequence

NPFFR2
NM_004885.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.29

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.016976357).

BP6

Variant 4-72138099-G-A is Benign according to our data. Variant chr4-72138099-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 734803.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
NPFFR2	NM_004885.3 linkuse as main transcript	c.388G>A	p.Ala130Thr	missense_variant	3/4	ENST00000308744.12
NPFFR2	NM_001144756.2 linkuse as main transcript	c.397G>A	p.Ala133Thr	missense_variant	4/5
NPFFR2	NM_053036.3 linkuse as main transcript	c.388G>A	p.Ala130Thr	missense_variant	3/4
NPFFR2	XM_011531554.3 linkuse as main transcript	c.364G>A	p.Ala122Thr	missense_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPFFR2	ENST00000308744.12 linkuse as main transcript	c.388G>A	p.Ala130Thr	missense_variant	3/4	1	NM_004885.3	P4	Q9Y5X5-2
NPFFR2	ENST00000395999.5 linkuse as main transcript	c.397G>A	p.Ala133Thr	missense_variant	4/5	1		A2	Q9Y5X5-3
NPFFR2	ENST00000358749.3 linkuse as main transcript	c.388G>A	p.Ala130Thr	missense_variant	3/4	1		P4	Q9Y5X5-2
NPFFR2	ENST00000344413.6 linkuse as main transcript	c.40G>A	p.Ala14Thr	missense_variant	2/3	1

Frequencies

GnomAD3 genomes

AF:

0.00189

AC:

287

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00659

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

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:

0.0000588

Gnomad OTH

AF:

0.000961

GnomAD3 exomes

AF:

0.000569

AC:

143

AN:

251134

Hom.:

AF XY:

0.000332

AC XY:

AN XY:

135736

show subpopulations

Gnomad AFR exome

AF:

0.00739

Gnomad AMR exome

AF:

0.000435

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000211

AC:

309

AN:

1461390

Hom.:

Cov.:

AF XY:

0.000182

AC XY:

132

AN XY:

727008

show subpopulations

Gnomad4 AFR exome

AF:

0.00640

Gnomad4 AMR exome

AF:

0.000560

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.000428

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.0000144

Gnomad4 OTH exome

AF:

0.000513

GnomAD4 genome

AF:

0.00188

AC:

287

AN:

152256

Hom.:

Cov.:

AF XY:

0.00162

AC XY:

121

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00657

Gnomad4 AMR

AF:

0.000524

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000951

Alfa

AF:

0.000476

Hom.:

Bravo

AF:

0.00240

ESP6500AA

AF:

0.00885

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000675

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 20, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0071

T;.;.

Eigen

Benign

0.014

Eigen_PC

Benign

0.076

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Benign

0.023

MetaRNN

Benign

0.017

T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.43

N;.;.

MutationTaster

Benign

0.99

D;D;D;N

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.62

N;N;N

REVEL

Benign

0.17

Sift

Benign

0.037

D;D;D

Sift4G

Benign

0.19

T;.;T

Polyphen

0.81

P;P;.

Vest4

0.59

MVP

0.75

MPC

0.13

ClinPred

0.065

GERP RS

4.4

Varity_R

0.087

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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