Variant 4-121332987-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_198179.3(QRFPR):c.631C>G(p.Gln211Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000312 in 1,581,994 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00031 ( 0 hom. )

Consequence

QRFPR
NM_198179.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.27

Variant links:

Genes affected

QRFPR (HGNC:15565): (pyroglutamylated RFamide peptide receptor) Enables G protein-coupled receptor activity. Involved in G protein-coupled receptor signaling pathway. Predicted to be located in non-motile cilium. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

QRFPR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06750369).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
QRFPR	NM_198179.3 linkuse as main transcript	c.631C>G	p.Gln211Glu	missense_variant	4/6	ENST00000394427.3	NP_937822.2	Q96P65

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
QRFPR	ENST00000394427.3 linkuse as main transcript	c.631C>G	p.Gln211Glu	missense_variant	4/6	1	NM_198179.3	ENSP00000377948.2	Q96P65
QRFPR	ENST00000334383.9 linkuse as main transcript	c.631C>G	p.Gln211Glu	missense_variant	4/6	2		ENSP00000335610.5	J3KNR3
QRFPR	ENST00000507331.5 linkuse as main transcript	n.*189C>G		non_coding_transcript_exon_variant	5/7	2		ENSP00000423369.1	F2Z3L3
QRFPR	ENST00000507331.5 linkuse as main transcript	n.*189C>G		3_prime_UTR_variant	5/7	2		ENSP00000423369.1	F2Z3L3

Frequencies

GnomAD3 genomes

AF:

0.000322

AC:

AN:

121086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000124

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000496

Gnomad ASJ

AF:

0.000723

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000443

Gnomad OTH

AF:

0.00190

GnomAD3 exomes

AF:

0.000398

AC:

100

AN:

251250

Hom.:

AF XY:

0.000427

AC XY:

AN XY:

135772

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.000636

Gnomad ASJ exome

AF:

0.00109

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000502

Gnomad OTH exome

AF:

0.000816

GnomAD4 exome

AF:

0.000311

AC:

454

AN:

1460788

Hom.:

Cov.:

AF XY:

0.000325

AC XY:

236

AN XY:

726644

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000560

Gnomad4 ASJ exome

AF:

0.000919

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000697

Gnomad4 FIN exome

AF:

0.000112

Gnomad4 NFE exome

AF:

0.000324

Gnomad4 OTH exome

AF:

0.000381

GnomAD4 genome

AF:

0.000322

AC:

AN:

121206

Hom.:

Cov.:

AF XY:

0.000233

AC XY:

AN XY:

60064

show subpopulations

Gnomad4 AFR

AF:

0.000123

Gnomad4 AMR

AF:

0.000495

Gnomad4 ASJ

AF:

0.000723

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000443

Gnomad4 OTH

AF:

0.00187

Alfa

AF:

0.000463

Hom.:

Bravo

AF:

0.000378

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000445

AC:

EpiCase

AF:

0.000655

EpiControl

AF:

0.000830

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 27, 2024

The c.631C>G (p.Q211E) alteration is located in exon 4 (coding exon 4) of the QRFPR gene. This alteration results from a C to G substitution at nucleotide position 631, causing the glutamine (Q) at amino acid position 211 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.032

.;T

Eigen

Benign

0.17

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.81

T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.068

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.50

.;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.82

N;N

REVEL

Benign

0.17

Sift

Benign

0.25

T;D

Sift4G

Uncertain

0.032

D;T

Polyphen

0.39

.;B

Vest4

0.34

MVP

0.64

MPC

0.029

ClinPred

0.035

GERP RS

6.1

Varity_R

0.57

gMVP

0.76

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