Variant 4-72146992-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004885.3(NPFFR2):c.443T>C(p.Val148Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00166 in 1,612,162 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0083 ( 28 hom., cov: 32)

Exomes 𝑓: 0.00097 ( 20 hom. )

Consequence

NPFFR2
NM_004885.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 7.89

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009416938).

BP6

Variant 4-72146992-T-C is Benign according to our data. Variant chr4-72146992-T-C is described in ClinVar as [Benign]. Clinvar id is 775989.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00829 (1262/152268) while in subpopulation AFR AF= 0.029 (1205/41526). AF 95% confidence interval is 0.0277. There are 28 homozygotes in gnomad4. There are 611 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 28 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPFFR2	NM_004885.3 linkuse as main transcript	c.443T>C	p.Val148Ala	missense_variant	4/4	ENST00000308744.12	NP_004876.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPFFR2	ENST00000308744.12 linkuse as main transcript	c.443T>C	p.Val148Ala	missense_variant	4/4	1	NM_004885.3	ENSP00000307822	P4	Q9Y5X5-2

Frequencies

GnomAD3 genomes

AF:

0.00830

AC:

1263

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0291

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.00289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00527

GnomAD3 exomes

AF:

0.00219

AC:

547

AN:

250084

Hom.:

AF XY:

0.00174

AC XY:

235

AN XY:

135136

show subpopulations

Gnomad AFR exome

AF:

0.0279

Gnomad AMR exome

AF:

0.00104

Gnomad ASJ exome

AF:

0.00392

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000133

Gnomad OTH exome

AF:

0.000492

GnomAD4 exome

AF:

0.000974

AC:

1422

AN:

1459894

Hom.:

Cov.:

AF XY:

0.000858

AC XY:

623

AN XY:

726140

show subpopulations

Gnomad4 AFR exome

AF:

0.0325

Gnomad4 AMR exome

AF:

0.00121

Gnomad4 ASJ exome

AF:

0.00281

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000432

Gnomad4 OTH exome

AF:

0.00222

GnomAD4 genome

AF:

0.00829

AC:

1262

AN:

152268

Hom.:

Cov.:

AF XY:

0.00820

AC XY:

611

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0290

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.00289

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00199

Hom.:

Bravo

AF:

0.00895

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0277

AC:

122

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00270

AC:

328

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.098

T;.;.

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.77

T;T;T

MetaRNN

Benign

0.0094

T;T;T

MetaSVM

Benign

-0.72

MutationAssessor

Uncertain

2.7

M;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-3.8

D;D;D

REVEL

Uncertain

0.42

Sift

Uncertain

0.0060

D;D;D

Sift4G

Uncertain

0.0030

D;.;D

Polyphen

0.97

D;P;.

Vest4

0.70

MVP

0.58

MPC

0.21

ClinPred

0.036

GERP RS

5.8

Varity_R

0.36

gMVP

0.85

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