20-56248494-A-G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MC3R	NM_019888.3	c.-350A>G		upstream_gene_variant		ENST00000243911.2	NP_063941.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MC3R	ENST00000243911.2	c.-350A>G		upstream_gene_variant		6	NM_019888.3	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

Gnomad4 AFR AF: 0.0192

Gnomad4 AMR AF: 0.0595

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.0644

Gnomad4 SAS AF: 0.0809

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.0840

Alfa AF: 0.104 Hom.: 115

Bravo AF: 0.0739

Asia WGS AF: 0.0660 AC: 229 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.5
DANN	Benign	0.56

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11575886; hg19: chr20-54823550;