Variant 18-13883021-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000529.2(MC2R):c.*1604G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0268 in 152,424 control chromosomes in the GnomAD database, including 67 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 67 hom., cov: 33)

Exomes 𝑓: 0.020 ( 0 hom. )

Consequence

MC2R
NM_000529.2 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0770

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 18-13883021-C-G is Benign according to our data. Variant chr18-13883021-C-G is described in ClinVar as [Benign]. Clinvar id is 326138.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0268 (4079/152326) while in subpopulation SAS AF= 0.0548 (265/4832). AF 95% confidence interval is 0.0494. There are 67 homozygotes in gnomad4. There are 2024 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 67 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
MC2R	NM_000529.2 linkuse as main transcript	c.*1604G>C	3_prime_UTR_variant	2/2	ENST00000327606.4
MC2R	NM_001291911.1 linkuse as main transcript	c.*1604G>C	3_prime_UTR_variant	2/2
MC2R	XM_017025781.2 linkuse as main transcript	c.*1604G>C	3_prime_UTR_variant	3/3
MC2R	XM_047437537.1 linkuse as main transcript	c.*1604G>C	3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MC2R	ENST00000327606.4 linkuse as main transcript	c.*1604G>C		3_prime_UTR_variant	2/2	1	NM_000529.2	P1

Frequencies

GnomAD3 genomes

AF:

0.0267

AC:

4066

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0236

Gnomad AMI

AF:

0.106

Gnomad AMR

AF:

0.0272

Gnomad ASJ

AF:

0.0271

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0550

Gnomad FIN

AF:

0.0141

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0293

Gnomad OTH

AF:

0.0272

GnomAD4 exome

AF:

0.0204

AC:

AN:

Hom.:

Cov.:

AF XY:

0.0244

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0244

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0268

AC:

4079

AN:

152326

Hom.:

Cov.:

AF XY:

0.0272

AC XY:

2024

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0239

Gnomad4 AMR

AF:

0.0271

Gnomad4 ASJ

AF:

0.0271

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.0548

Gnomad4 FIN

AF:

0.0141

Gnomad4 NFE

AF:

0.0294

Gnomad4 OTH

AF:

0.0269

Alfa

AF:

0.00402

Hom.:

Bravo

AF:

0.0270

Asia WGS

AF:

0.0250

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Glucocorticoid deficiency 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

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

-0.86

CADD

Benign

1.3

DANN

Benign

0.71

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over