rs1541276

Positions:

• chr18-13825728-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005913.3(MC5R):​c.-38A>C variant causes a splice region, 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 1,521,010 control chromosomes in the GnomAD database, including 22,011 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.18 (2671 hom., cov: 31)
  • Exomes 𝑓: 0.17 (19340 hom.)
• Consequence: MC5R NM_005913.3 splice_region, 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MC5R	NM_005913.3	c.-38A>C		splice_region_variant, 5_prime_UTR_variant	2/2	ENST00000589410.2	NP_005904.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MC5R	ENST00000589410.2	c.-38A>C		splice_region_variant, 5_prime_UTR_variant	2/2	3	NM_005913.3	ENSP00000468086	P1
MC5R	ENST00000324750.5	c.-38A>C		5_prime_UTR_variant	1/1			ENSP00000318077	P1

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28080 AN: 151986 Hom.: 2664 Cov.: 31

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.0847

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.171

GnomAD3 exomes AF: 0.174 AC: 31756 AN: 182540 Hom.: 2895 AF XY: 0.170 AC XY: 16364 AN XY: 96324

Gnomad AFR exome AF: 0.213

Gnomad AMR exome AF: 0.205

Gnomad ASJ exome AF: 0.154

Gnomad EAS exome AF: 0.224

Gnomad SAS exome AF: 0.0873

Gnomad FIN exome AF: 0.171

Gnomad NFE exome AF: 0.167

Gnomad OTH exome AF: 0.174

GnomAD4 exome AF: 0.166 AC: 226564 AN: 1368906 Hom.: 19340 Cov.: 29 AF XY: 0.164 AC XY: 110137 AN XY: 673600

Gnomad4 AFR exome AF: 0.210

Gnomad4 AMR exome AF: 0.210

Gnomad4 ASJ exome AF: 0.154

Gnomad4 EAS exome AF: 0.231

Gnomad4 SAS exome AF: 0.0883

Gnomad4 FIN exome AF: 0.169

Gnomad4 NFE exome AF: 0.165

Gnomad4 OTH exome AF: 0.169

GnomAD4 genome AF: 0.185 AC: 28108 AN: 152104 Hom.: 2671 Cov.: 31 AF XY: 0.185 AC XY: 13742 AN XY: 74342

Gnomad4 AFR AF: 0.210

Gnomad4 AMR AF: 0.212

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.230

Gnomad4 SAS AF: 0.0850

Gnomad4 FIN AF: 0.177

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.171

Alfa AF: 0.174 Hom.: 953

Bravo AF: 0.190

Asia WGS AF: 0.157 AC: 547 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	5.5
DANN	Benign	0.86

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

Other links and lift over

dbSNP: rs1541276; hg19: chr18-13825727; COSMIC: COSV61254750;