chr20-56248494-A-G

Variant names:

• chr20-56248494-A-G
• rs11575886
• NM_019888.3:c.-350A>G

Variant summary

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

The NM_019888.3(MC3R):​c.-350A>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0805 in 152,240 control chromosomes in the GnomAD database, including 648 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 0.080 (648 hom., cov: 32)
• Consequence: MC3R NM_019888.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.566
• Publications: 2 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019888.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MC3R	NM_019888.3	MANE Select	c.-350A>G		upstream_gene	N/A	NP_063941.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MC3R	ENST00000243911.2	TSL:6 MANE Select	c.-350A>G		upstream_gene	N/A	ENSP00000243911.2

Frequencies

GnomAD3 genomes AF: 0.0806 AC: 12261 AN: 152122 Hom.: 649 Cov.: 32

Gnomad AFR AF: 0.0193

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.0597

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.0648

Gnomad SAS AF: 0.0806

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.0853

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0805 AC: 12252 AN: 152240 Hom.: 648 Cov.: 32 AF XY: 0.0804 AC XY: 5985 AN XY: 74424

African (AFR) AF: 0.0192 AC: 798 AN: 41570

American (AMR) AF: 0.0595 AC: 911 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 566 AN: 3468

East Asian (EAS) AF: 0.0644 AC: 333 AN: 5170

South Asian (SAS) AF: 0.0809 AC: 390 AN: 4822

European-Finnish (FIN) AF: 0.109 AC: 1158 AN: 10596

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7827 AN: 68000

Other (OTH) AF: 0.0840 AC: 177 AN: 2108

Alfa AF: 0.0710 Hom.: 217

Bravo AF: 0.0739

Asia WGS AF: 0.0660 AC: 229 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.5
DANN	Benign	0.56
PhyloP100		-0.57
PromoterAI		-0.0066	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11575886; hg19: chr20-54823550;