NM_005913.3:c.-38A>C

Variant names:

• chr18-13825728-A-C
• rs1541276
• NM_005913.3:c.-38A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005913.3(MC5R):​c.-38A>C variant causes a splice region 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MC5R	NM_005913.3	c.-38A>C		splice_region_variant	Exon 2 of 2	ENST00000589410.2	NP_005904.1
MC5R	NM_005913.3	c.-38A>C		5_prime_UTR_variant	Exon 2 of 2	ENST00000589410.2	NP_005904.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MC5R	ENST00000589410.2	c.-38A>C		splice_region_variant	Exon 2 of 2	3	NM_005913.3	ENSP00000468086.2
MC5R	ENST00000589410.2	c.-38A>C		5_prime_UTR_variant	Exon 2 of 2	3	NM_005913.3	ENSP00000468086.2
MC5R	ENST00000324750.5	c.-38A>C		5_prime_UTR_variant	Exon 1 of 1	6		ENSP00000318077.3

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

GnomAD2 exomes AF: 0.174 AC: 31756 AN: 182540 AF XY: 0.170

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 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

African (AFR) AF: 0.210 AC: 6340 AN: 30248

American (AMR) AF: 0.210 AC: 6342 AN: 30146

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 3128 AN: 20364

East Asian (EAS) AF: 0.231 AC: 9029 AN: 39056

South Asian (SAS) AF: 0.0883 AC: 6275 AN: 71026

European-Finnish (FIN) AF: 0.169 AC: 8443 AN: 50054

Middle Eastern (MID) AF: 0.193 AC: 1031 AN: 5336

European-Non Finnish (NFE) AF: 0.165 AC: 176464 AN: 1066312

Other (OTH) AF: 0.169 AC: 9512 AN: 56364

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

African (AFR) AF: 0.210 AC: 8723 AN: 41462

American (AMR) AF: 0.212 AC: 3242 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 522 AN: 3472

East Asian (EAS) AF: 0.230 AC: 1191 AN: 5168

South Asian (SAS) AF: 0.0850 AC: 410 AN: 4822

European-Finnish (FIN) AF: 0.177 AC: 1872 AN: 10582

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11580 AN: 68002

Other (OTH) AF: 0.171 AC: 362 AN: 2112

Alfa AF: 0.174 Hom.: 1149

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
PhyloP100		1.5
PromoterAI		0.0017	Neutral
Mutation Taster		=298/2	polymorphism (auto)

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

Other links and lift over

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