rs1941088

Positions:

• chr18-13914914-G-A
• chr18-13914914-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000529.2(MC2R):​c.-129+574C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 152,126 control chromosomes in the GnomAD database, including 13,600 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 0.41 (13600 hom., cov: 33)
• Consequence: MC2R NM_000529.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.561 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MC2R	NM_000529.2	c.-129+574C>T		intron_variant		ENST00000327606.4
MC2R	NM_001291911.1	c.-129+716C>T		intron_variant
MC2R	XM_017025781.2	c.-661+574C>T		intron_variant
MC2R	XM_047437537.1	c.-818+574C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MC2R	ENST00000327606.4	c.-129+574C>T		intron_variant		1	NM_000529.2	P1
MC2R	ENST00000399821.2	c.-129+716C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62157 AN: 152008 Hom.: 13579 Cov.: 33

Gnomad AFR AF: 0.567

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.394

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

GnomAD4 genome AF: 0.409 AC: 62217 AN: 152126 Hom.: 13600 Cov.: 33 AF XY: 0.407 AC XY: 30288 AN XY: 74368

Gnomad4 AFR AF: 0.567

Gnomad4 AMR AF: 0.355

Gnomad4 ASJ AF: 0.379

Gnomad4 EAS AF: 0.208

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.384

Gnomad4 NFE AF: 0.362

Gnomad4 OTH AF: 0.388

Alfa AF: 0.366 Hom.: 10360

Bravo AF: 0.417

Asia WGS AF: 0.239 AC: 835 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.13
DANN	Benign	0.73

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: rs1941088; hg19: chr18-13914913;