rs4797825

Variant names:

• chr18-13884567-C-T
• rs4797825
• NM_000529.2:c.*58G>A

Your query was ambiguous. Multiple possible variants found:

• chr18-13884567-C-T
• chr18-13884567-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000529.2(MC2R):​c.*58G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 1,574,826 control chromosomes in the GnomAD database, including 184,865 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (24192 hom., cov: 31)
  • Exomes 𝑓: 0.47 (160673 hom.)
• Consequence: MC2R NM_000529.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0850
• Publications: 16 publications found

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]

MC2R Gene-Disease associations (from GenCC):

• glucocorticoid deficiency 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• familial glucocorticoid deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 18-13884567-C-T is Benign according to our data. Variant chr18-13884567-C-T is described in ClinVar as Benign. ClinVar VariationId is 326189.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000529.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MC2R	NM_000529.2	MANE Select	c.*58G>A		3_prime_UTR	Exon 2 of 2	NP_000520.1	Q01718
	MC2R	NM_001291911.1		c.*58G>A		3_prime_UTR	Exon 2 of 2	NP_001278840.1	Q01718

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MC2R	ENST00000327606.4	TSL:1 MANE Select	c.*58G>A		3_prime_UTR	Exon 2 of 2	ENSP00000333821.2	Q01718
	MC2R	ENST00000946323.1		c.*58G>A		3_prime_UTR	Exon 3 of 3	ENSP00000616382.1
	MC2R	ENST00000946324.1		c.*58G>A		3_prime_UTR	Exon 3 of 3	ENSP00000616383.1

Frequencies

GnomAD3 genomes AF: 0.550 AC: 83470 AN: 151826 Hom.: 24157 Cov.: 31

Gnomad AFR AF: 0.744

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.498

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.526

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.478

Gnomad OTH AF: 0.541

GnomAD4 exome AF: 0.471 AC: 669502 AN: 1422880 Hom.: 160673 Cov.: 26 AF XY: 0.467 AC XY: 331604 AN XY: 710242

African (AFR) AF: 0.754 AC: 24755 AN: 32822

American (AMR) AF: 0.437 AC: 19516 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 13281 AN: 25956

East Asian (EAS) AF: 0.452 AC: 17846 AN: 39524

South Asian (SAS) AF: 0.343 AC: 29336 AN: 85434

European-Finnish (FIN) AF: 0.533 AC: 23950 AN: 44960

Middle Eastern (MID) AF: 0.582 AC: 2390 AN: 4108

European-Non Finnish (NFE) AF: 0.469 AC: 509673 AN: 1086148

Other (OTH) AF: 0.485 AC: 28755 AN: 59270

GnomAD4 genome AF: 0.550 AC: 83545 AN: 151946 Hom.: 24192 Cov.: 31 AF XY: 0.549 AC XY: 40787 AN XY: 74260

African (AFR) AF: 0.744 AC: 30835 AN: 41446

American (AMR) AF: 0.493 AC: 7541 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.498 AC: 1729 AN: 3472

East Asian (EAS) AF: 0.409 AC: 2101 AN: 5132

South Asian (SAS) AF: 0.329 AC: 1584 AN: 4818

European-Finnish (FIN) AF: 0.526 AC: 5542 AN: 10532

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.478 AC: 32448 AN: 67948

Other (OTH) AF: 0.534 AC: 1127 AN: 2110

Alfa AF: 0.492 Hom.: 10305

Bravo AF: 0.557

Asia WGS AF: 0.383 AC: 1336 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Glucocorticoid deficiency 1 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.3
DANN	Benign	0.78
PhyloP100		-0.085
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4797825; hg19: chr18-13884566; COSMIC: COSV59617457; COSMIC: COSV59617457;