chr18-13883940-C-T

Variant names:

• chr18-13883940-C-T
• rs4308014
• NM_000529.2:c.*685G>A

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.*685G>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 0.549 in 154,414 control chromosomes in the GnomAD database, including 24,645 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (24447 hom., cov: 32)
  • Exomes 𝑓: 0.39 (198 hom.)
• Consequence: MC2R NM_000529.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.647
• Publications: 10 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=-0.93).
• BP6: Variant 18-13883940-C-T is Benign according to our data. Variant chr18-13883940-C-T is described in ClinVar as Benign. ClinVar VariationId is 326174.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.744 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.*685G>A		3_prime_UTR	Exon 2 of 2	NP_000520.1	Q01718
	MC2R	NM_001291911.1		c.*685G>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.*685G>A		3_prime_UTR	Exon 2 of 2	ENSP00000333821.2	Q01718
	MC2R	ENST00000946323.1		c.*685G>A		3_prime_UTR	Exon 3 of 3	ENSP00000616382.1
	MC2R	ENST00000946324.1		c.*685G>A		3_prime_UTR	Exon 3 of 3	ENSP00000616383.1

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83858 AN: 151952 Hom.: 24409 Cov.: 32

Gnomad AFR AF: 0.751

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: 0.527

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.478

Gnomad OTH AF: 0.542

GnomAD4 exome AF: 0.388 AC: 910 AN: 2344 Hom.: 198 Cov.: 0 AF XY: 0.386 AC XY: 468 AN XY: 1212

African (AFR) AF: 0.500 AC: 2 AN: 4

American (AMR) AF: 0.385 AC: 222 AN: 576

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 4 AN: 6

East Asian (EAS) AF: 0.346 AC: 9 AN: 26

South Asian (SAS) AF: 0.290 AC: 47 AN: 162

European-Finnish (FIN) AF: 0.667 AC: 4 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.400 AC: 594 AN: 1486

Other (OTH) AF: 0.359 AC: 28 AN: 78

GnomAD4 genome AF: 0.552 AC: 83940 AN: 152070 Hom.: 24447 Cov.: 32 AF XY: 0.551 AC XY: 40965 AN XY: 74328

African (AFR) AF: 0.751 AC: 31179 AN: 41498

American (AMR) AF: 0.494 AC: 7547 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.498 AC: 1727 AN: 3468

East Asian (EAS) AF: 0.409 AC: 2115 AN: 5166

South Asian (SAS) AF: 0.329 AC: 1585 AN: 4820

European-Finnish (FIN) AF: 0.527 AC: 5560 AN: 10548

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

European-Non Finnish (NFE) AF: 0.478 AC: 32461 AN: 67970

Other (OTH) AF: 0.535 AC: 1130 AN: 2112

Alfa AF: 0.505 Hom.: 63425

Bravo AF: 0.560

Asia WGS AF: 0.385 AC: 1343 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	-0.93
CADD	Benign	5.1
DANN	Benign	0.52
PhyloP100		0.65
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: rs4308014; hg19: chr18-13883939;