Variant rs2236700 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005913.3(MC5R):c.627C>G(p.Phe209Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 1,613,898 control chromosomes in the GnomAD database, including 32,421 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.23 ( 4230 hom., cov: 32)

Exomes 𝑓: 0.19 ( 28191 hom. )

Consequence

MC5R
NM_005913.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.86

Variant links:

Genes affected

MC5R (HGNC:6933): (melanocortin 5 receptor) This gene encodes a member of the seven-pass transmembrane G protein-coupled melanocortin receptor protein family that stimulate cAMP signal transduction. The encoded protein is a receptor for melanocyte-stimulating hormone and adrenocorticotropic hormone and is suggested to play a role in sebum generation. [provided by RefSeq, Jun 2010]

MC5R links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018680692).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MC5R	NM_005913.3 linkuse as main transcript	c.627C>G	p.Phe209Leu	missense_variant	2/2	ENST00000589410.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MC5R	ENST00000589410.2 linkuse as main transcript	c.627C>G	p.Phe209Leu	missense_variant	2/2	3	NM_005913.3	P1
MC5R	ENST00000324750.5 linkuse as main transcript	c.627C>G	p.Phe209Leu	missense_variant	1/1			P1

Frequencies

GnomAD3 genomes

AF:

0.229

AC:

34763

AN:

151962

Hom.:

4222

Cov.:

show subpopulations

Gnomad AFR

AF:

0.299

Gnomad AMI

AF:

0.164

Gnomad AMR

AF:

0.279

Gnomad ASJ

AF:

0.176

Gnomad EAS

AF:

0.362

Gnomad SAS

AF:

0.137

Gnomad FIN

AF:

0.173

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.184

Gnomad OTH

AF:

0.214

GnomAD3 exomes

AF:

0.211

AC:

52947

AN:

251228

Hom.:

6157

AF XY:

0.202

AC XY:

27385

AN XY:

135750

show subpopulations

Gnomad AFR exome

AF:

0.304

Gnomad AMR exome

AF:

0.292

Gnomad ASJ exome

AF:

0.177

Gnomad EAS exome

AF:

0.350

Gnomad SAS exome

AF:

0.143

Gnomad FIN exome

AF:

0.175

Gnomad NFE exome

AF:

0.179

Gnomad OTH exome

AF:

0.202

GnomAD4 exome

AF:

0.190

AC:

278089

AN:

1461818

Hom.:

28191

Cov.:

AF XY:

0.188

AC XY:

136627

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.306

Gnomad4 AMR exome

AF:

0.293

Gnomad4 ASJ exome

AF:

0.176

Gnomad4 EAS exome

AF:

0.385

Gnomad4 SAS exome

AF:

0.141

Gnomad4 FIN exome

AF:

0.172

Gnomad4 NFE exome

AF:

0.180

Gnomad4 OTH exome

AF:

0.200

GnomAD4 genome

AF:

0.229

AC:

34807

AN:

152080

Hom.:

4230

Cov.:

AF XY:

0.227

AC XY:

16848

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.299

Gnomad4 AMR

AF:

0.279

Gnomad4 ASJ

AF:

0.176

Gnomad4 EAS

AF:

0.363

Gnomad4 SAS

AF:

0.137

Gnomad4 FIN

AF:

0.173

Gnomad4 NFE

AF:

0.184

Gnomad4 OTH

AF:

0.213

Alfa

AF:

0.193

Hom.:

2238

Bravo

AF:

0.243

TwinsUK

AF:

0.175

AC:

650

ALSPAC

AF:

0.173

AC:

667

ESP6500AA

AF:

0.296

AC:

1304

ESP6500EA

AF:

0.179

AC:

1537

ExAC

AF:

0.207

AC:

25121

Asia WGS

AF:

0.245

AC:

850

AN:

3478

EpiCase

AF:

0.185

EpiControl

AF:

0.186

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.87

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.40

T;T

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.87

.;D

MetaRNN

Benign

0.0019

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.5

M;M

MutationTaster

Benign

0.0000016

PrimateAI

Uncertain

0.67

PROVEAN

Pathogenic

-4.7

.;D

REVEL

Benign

0.15

Sift

Pathogenic

0.0

.;D

Sift4G

Benign

0.12

.;T

Polyphen

1.0

D;D

Vest4

0.35

MutPred

0.24

Gain of MoRF binding (P = 0.1879);Gain of MoRF binding (P = 0.1879);

MPC

0.94

ClinPred

0.025

GERP RS

3.2

Varity_R

0.92

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over