Variant chr18-13826140-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_005913.3(MC5R):c.375C>T(p.Ser125Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 1,614,126 control chromosomes in the GnomAD database, including 115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0085 ( 10 hom., cov: 32)

Exomes 𝑓: 0.011 ( 105 hom. )

Consequence

MC5R
NM_005913.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.66

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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 18-13826140-C-T is Benign according to our data. Variant chr18-13826140-C-T is described in ClinVar as [Benign]. Clinvar id is 777720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.66 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MC5R	NM_005913.3 linkuse as main transcript	c.375C>T	p.Ser125Ser	synonymous_variant	2/2	ENST00000589410.2	NP_005904.1	P33032

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MC5R	ENST00000589410.2 linkuse as main transcript	c.375C>T	p.Ser125Ser	synonymous_variant	2/2	3	NM_005913.3	ENSP00000468086.2		P33032
MC5R	ENST00000324750.5 linkuse as main transcript	c.375C>T	p.Ser125Ser	synonymous_variant	1/1	6		ENSP00000318077.3		P33032

Frequencies

GnomAD3 genomes

AF:

0.00854

AC:

1300

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00191

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.00353

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.0190

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0133

Gnomad OTH

AF:

0.00957

GnomAD3 exomes

AF:

0.00914

AC:

2299

AN:

251440

Hom.:

AF XY:

0.00921

AC XY:

1252

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.00166

Gnomad AMR exome

AF:

0.00341

Gnomad ASJ exome

AF:

0.00556

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00242

Gnomad FIN exome

AF:

0.0175

Gnomad NFE exome

AF:

0.0139

Gnomad OTH exome

AF:

0.0101

GnomAD4 exome

AF:

0.0110

AC:

16047

AN:

1461852

Hom.:

105

Cov.:

AF XY:

0.0107

AC XY:

7746

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.00137

Gnomad4 AMR exome

AF:

0.00313

Gnomad4 ASJ exome

AF:

0.00467

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00278

Gnomad4 FIN exome

AF:

0.0177

Gnomad4 NFE exome

AF:

0.0125

Gnomad4 OTH exome

AF:

0.0102

GnomAD4 genome

AF:

0.00854

AC:

1300

AN:

152274

Hom.:

Cov.:

AF XY:

0.00845

AC XY:

629

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00190

Gnomad4 AMR

AF:

0.00353

Gnomad4 ASJ

AF:

0.00432

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00125

Gnomad4 FIN

AF:

0.0190

Gnomad4 NFE

AF:

0.0133

Gnomad4 OTH

AF:

0.00947

Alfa

AF:

0.0117

Hom.:

Bravo

AF:

0.00697

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.0105

EpiControl

AF:

0.0122

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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 21, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

0.54

DANN

Benign

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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