dbSNP rs2236700: MC5R:p.Phe209Leu (chr18-13826392-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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.

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

Publications

34 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MC5R	NM_005913.3 link	c.627C>G	p.Phe209Leu	missense_variant	Exon 2 of 2	ENST00000589410.2	NP_005904.1	P33032

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MC5R	ENST00000589410.2 link	c.627C>G	p.Phe209Leu	missense_variant	Exon 2 of 2	3	NM_005913.3	ENSP00000468086.2		P33032
MC5R	ENST00000324750.5 link	c.627C>G	p.Phe209Leu	missense_variant	Exon 1 of 1	6		ENSP00000318077.3		P33032

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

GnomAD2 exomes

AF:

0.211

AC:

52947

AN:

251228

AF XY:

0.202

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 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

African (AFR)

AF:

0.306

AC:

10236

AN:

33478

American (AMR)

AF:

0.293

AC:

13084

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.176

AC:

4611

AN:

26136

East Asian (EAS)

AF:

0.385

AC:

15298

AN:

39698

South Asian (SAS)

AF:

0.141

AC:

12149

AN:

86256

European-Finnish (FIN)

AF:

0.172

AC:

9177

AN:

53370

Middle Eastern (MID)

AF:

0.179

AC:

1031

AN:

5768

European-Non Finnish (NFE)

AF:

0.180

AC:

200405

AN:

1111996

Other (OTH)

AF:

0.200

AC:

12098

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

14866

29732

44597

59463

74329

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7242

14484

21726

28968

36210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.229

AC:

34807

AN:

152080

Hom.:

4230

Cov.:

AF XY:

0.227

AC XY:

16848

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.299

AC:

12406

AN:

41480

American (AMR)

AF:

0.279

AC:

4266

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.176

AC:

611

AN:

3468

East Asian (EAS)

AF:

0.363

AC:

1869

AN:

5142

South Asian (SAS)

AF:

0.137

AC:

663

AN:

4826

European-Finnish (FIN)

AF:

0.173

AC:

1831

AN:

10582

Middle Eastern (MID)

AF:

0.170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.184

AC:

12511

AN:

67982

Other (OTH)

AF:

0.213

AC:

450

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1369

2739

4108

5478

6847

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

346

692

1038

1384

1730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

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

PhyloP100

1.9

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

Mutation Taster

=85/15

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over