rs79533878

chr18-13915538-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001291911.1(MC2R):c.-129+92T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0849 in 153,106 control chromosomes in the GnomAD database, including 720 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.085 (713 hom., cov: 33)
  • Exomes 𝑓: 0.11 (7 hom.)
• Consequence: MC2R NM_001291911.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.520

Genes affected

MC2R (HGNC:6930): (melanocortin 2 receptor) MC2R encodes one member of the five-member G-protein associated melanocortin receptor family. Melanocortins (melanocyte-stimulating hormones and adrenocorticotropic hormone) are peptides derived from pro-opiomelanocortin (POMC). MC2R is selectively activated by adrenocorticotropic hormone, whereas the other four melanocortin receptors recognize a variety of melanocortin ligands. Mutations in MC2R can result in familial glucocorticoid deficiency. Alternate transcript variants have been found for this gene. [provided by RefSeq, May 2014]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 18-13915538-A-G is Benign according to our data. Variant chr18-13915538-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 369249.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MC2R	NM_001291911.1	c.-129+92T>C		intron_variant
MC2R	NM_000529.2			upstream_gene_variant		ENST00000327606.4
MC2R	XM_017025781.2			upstream_gene_variant
MC2R	XM_047437537.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MC2R	ENST00000399821.2	c.-129+92T>C		intron_variant		3
MC2R	ENST00000327606.4			upstream_gene_variant		1	NM_000529.2	P1

Frequencies

GnomAD3 genomes AF: 0.0849 AC: 12920 AN: 152156 Hom.: 714 Cov.: 33

Gnomad AFR AF: 0.0317

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.0810

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.0637

Gnomad FIN AF: 0.0901

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.0755

GnomAD4 exome AF: 0.106 AC: 88 AN: 832 Hom.: 7 Cov.: 0 AF XY: 0.119 AC XY: 57 AN XY: 478

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0556

Gnomad4 EAS exome AF: 0.310

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0949

Gnomad4 NFE exome AF: 0.0923

Gnomad4 OTH exome AF: 0.143

GnomAD4 genome AF: 0.0848 AC: 12915 AN: 152274 Hom.: 713 Cov.: 33 AF XY: 0.0851 AC XY: 6335 AN XY: 74462

Gnomad4 AFR AF: 0.0317

Gnomad4 AMR AF: 0.120

Gnomad4 ASJ AF: 0.0810

Gnomad4 EAS AF: 0.187

Gnomad4 SAS AF: 0.0636

Gnomad4 FIN AF: 0.0901

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.0738

Alfa AF: 0.0844 Hom.: 91

Bravo AF: 0.0876

Asia WGS AF: 0.125 AC: 435 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Glucocorticoid Deficiency Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	2.1
Dann	Benign	0.29

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: rs79533878; hg19: chr18-13915537; COSMIC: COSV59619170; COSMIC: COSV59619170;