rs3746619

Positions:

• chr20-56248749-C-A
• chr20-56248749-C-T

Variant summary

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

The NM_019888.3(MC3R):​c.-95C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 1,416,136 control chromosomes in the GnomAD database, including 16,349 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 0.20 (5182 hom., cov: 32)
  • Exomes 𝑓: 0.11 (11167 hom.)
• Consequence: MC3R NM_019888.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.245

Genes affected

MC3R (HGNC:6931): (melanocortin 3 receptor) This gene encodes a G-protein-coupled receptor for melanocyte-stimulating hormone and adrenocorticotropic hormone that is expressed in tissues other than the adrenal cortex and melanocytes. This gene maps to the same region as the locus for benign neonatal epilepsy. Mice deficient for this gene have increased fat mass despite decreased food intake, suggesting a role for this gene product in the regulation of energy homeostasis. Mutations in this gene are associated with a susceptibility to obesity in humans. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MC3R	NM_019888.3	c.-95C>A		5_prime_UTR_variant	1/1	ENST00000243911.2	NP_063941.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MC3R	ENST00000243911.2	c.-95C>A		5_prime_UTR_variant	1/1		NM_019888.3	ENSP00000243911	P1

Frequencies

GnomAD3 genomes AF: 0.204 AC: 31015 AN: 152022 Hom.: 5160 Cov.: 32

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.0970

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.0880

Gnomad OTH AF: 0.158

GnomAD3 exomes AF: 0.142 AC: 35658 AN: 251022 Hom.: 3944 AF XY: 0.140 AC XY: 18949 AN XY: 135754

Gnomad AFR exome AF: 0.470

Gnomad AMR exome AF: 0.0936

Gnomad ASJ exome AF: 0.101

Gnomad EAS exome AF: 0.231

Gnomad SAS exome AF: 0.216

Gnomad FIN exome AF: 0.0951

Gnomad NFE exome AF: 0.0894

Gnomad OTH exome AF: 0.122

GnomAD4 exome AF: 0.111 AC: 139788 AN: 1263996 Hom.: 11167 Cov.: 18 AF XY: 0.113 AC XY: 72277 AN XY: 639144

Gnomad4 AFR exome AF: 0.469

Gnomad4 AMR exome AF: 0.0945

Gnomad4 ASJ exome AF: 0.103

Gnomad4 EAS exome AF: 0.238

Gnomad4 SAS exome AF: 0.213

Gnomad4 FIN exome AF: 0.0989

Gnomad4 NFE exome AF: 0.0850

Gnomad4 OTH exome AF: 0.131

GnomAD4 genome AF: 0.204 AC: 31097 AN: 152140 Hom.: 5182 Cov.: 32 AF XY: 0.202 AC XY: 15055 AN XY: 74366

Gnomad4 AFR AF: 0.461

Gnomad4 AMR AF: 0.117

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.235

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.0970

Gnomad4 NFE AF: 0.0880

Gnomad4 OTH AF: 0.164

Alfa AF: 0.109 Hom.: 3145

Bravo AF: 0.215

Asia WGS AF: 0.246 AC: 856 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.5
DANN	Benign	0.76

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: rs3746619; hg19: chr20-54823805; COSMIC: COSV54765057;