chr18-13915543-G-A

Position:

• chr18-13915543-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001291911.1(MC2R):​c.-129+87C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0444 in 153,078 control chromosomes in the GnomAD database, including 341 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.045 (339 hom., cov: 33)
  • Exomes 𝑓: 0.017 (2 hom.)
• Consequence: MC2R NM_001291911.1 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.379

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 18-13915543-G-A is Benign according to our data. Variant chr18-13915543-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 369250.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MC2R	NM_001291911.1	c.-129+87C>T		intron_variant			NP_001278840.1
MC2R	NM_000529.2			upstream_gene_variant		ENST00000327606.4	NP_000520.1
MC2R	XM_017025781.2			upstream_gene_variant			XP_016881270.1
MC2R	XM_047437537.1			upstream_gene_variant			XP_047293493.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MC2R	ENST00000399821.2	c.-129+87C>T		intron_variant		3		ENSP00000382718
MC2R	ENST00000327606.4			upstream_gene_variant		1	NM_000529.2	ENSP00000333821	P1

Frequencies

GnomAD3 genomes AF: 0.0445 AC: 6772 AN: 152132 Hom.: 337 Cov.: 33

Gnomad AFR AF: 0.0983

Gnomad AMI AF: 0.0505

Gnomad AMR AF: 0.0683

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.0313

Gnomad FIN AF: 0.00575

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00470

Gnomad OTH AF: 0.0373

GnomAD4 exome AF: 0.0169 AC: 14 AN: 828 Hom.: 2 Cov.: 0 AF XY: 0.0106 AC XY: 5 AN XY: 470

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.167

Gnomad4 ASJ exome AF: 0.0556

Gnomad4 EAS exome AF: 0.263

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00391

Gnomad4 OTH exome AF: 0.0294

GnomAD4 genome AF: 0.0446 AC: 6786 AN: 152250 Hom.: 339 Cov.: 33 AF XY: 0.0460 AC XY: 3423 AN XY: 74432

Gnomad4 AFR AF: 0.0982

Gnomad4 AMR AF: 0.0682

Gnomad4 ASJ AF: 0.0153

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.0319

Gnomad4 FIN AF: 0.00575

Gnomad4 NFE AF: 0.00470

Gnomad4 OTH AF: 0.0384

Alfa AF: 0.0307 Hom.: 33

Bravo AF: 0.0522

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Glucocorticoid Deficiency Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	10
DANN	Benign	0.93

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2186944; hg19: chr18-13915542;