chr20-56248749-C-A

Variant names:

• chr20-56248749-C-A
• rs3746619
• NM_019888.3:c.-95C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 38 publications found

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]

MC3R Gene-Disease associations (from GenCC):

• body mass index quantitative trait locus 9

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MC3R	NM_019888.3	c.-95C>A		5_prime_UTR_variant	Exon 1 of 1	ENST00000243911.2	NP_063941.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MC3R	ENST00000243911.2	c.-95C>A		5_prime_UTR_variant	Exon 1 of 1	6	NM_019888.3	ENSP00000243911.2

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

GnomAD2 exomes AF: 0.142 AC: 35658 AN: 251022 AF XY: 0.140

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 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

African (AFR) AF: 0.469 AC: 13827 AN: 29488

American (AMR) AF: 0.0945 AC: 4202 AN: 44472

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 2574 AN: 24984

East Asian (EAS) AF: 0.238 AC: 9229 AN: 38782

South Asian (SAS) AF: 0.213 AC: 17479 AN: 81964

European-Finnish (FIN) AF: 0.0989 AC: 5275 AN: 53324

Middle Eastern (MID) AF: 0.172 AC: 926 AN: 5396

European-Non Finnish (NFE) AF: 0.0850 AC: 79194 AN: 931710

Other (OTH) AF: 0.131 AC: 7082 AN: 53876

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

African (AFR) AF: 0.461 AC: 19133 AN: 41474

American (AMR) AF: 0.117 AC: 1787 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 384 AN: 3470

East Asian (EAS) AF: 0.235 AC: 1215 AN: 5164

South Asian (SAS) AF: 0.216 AC: 1042 AN: 4814

European-Finnish (FIN) AF: 0.0970 AC: 1028 AN: 10602

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.0880 AC: 5983 AN: 68002

Other (OTH) AF: 0.164 AC: 346 AN: 2116

Alfa AF: 0.117 Hom.: 5569

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
PhyloP100		0.24
PromoterAI		-0.055	Neutral
Mutation Taster		=300/0	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: rs3746619; hg19: chr20-54823805; COSMIC: COSV54765057;