dbSNP rs1941088: MC2R:c.-129+574C>T (chr18-13914914-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.26

Publications

5 publications found

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 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

MC2R links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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	Effect	Exon rank	MANE	Protein	UniProt
MC2R	NM_000529.2 link	c.-129+574C>T	intron_variant	Intron 1 of 1	ENST00000327606.4	NP_000520.1	Q01718
MC2R	NM_001291911.1 link	c.-129+716C>T	intron_variant	Intron 1 of 1		NP_001278840.1	Q01718
MC2R	XM_017025781.2 link	c.-661+574C>T	intron_variant	Intron 1 of 2		XP_016881270.1	Q01718
MC2R	XM_047437537.1 link	c.-818+574C>T	intron_variant	Intron 1 of 3		XP_047293493.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MC2R	ENST00000327606.4 link	c.-129+574C>T		intron_variant	Intron 1 of 1	1	NM_000529.2	ENSP00000333821.2		Q01718
MC2R	ENST00000399821.2 link	c.-129+716C>T		intron_variant	Intron 1 of 1	3		ENSP00000382718.2		R4GMM0

Frequencies

GnomAD3 genomes

AF:

0.409

AC:

62157

AN:

152008

Hom.:

13579

Cov.:

show subpopulations

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.:

AF XY:

0.407

AC XY:

30288

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.567

AC:

23521

AN:

41488

American (AMR)

AF:

0.355

AC:

5430

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.379

AC:

1317

AN:

3472

East Asian (EAS)

AF:

0.208

AC:

1079

AN:

5180

South Asian (SAS)

AF:

0.203

AC:

978

AN:

4824

European-Finnish (FIN)

AF:

0.384

AC:

4057

AN:

10564

Middle Eastern (MID)

AF:

0.459

AC:

135

AN:

294

European-Non Finnish (NFE)

AF:

0.362

AC:

24581

AN:

67986

Other (OTH)

AF:

0.388

AC:

819

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1844

3688

5532

7376

9220

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

558

1116

1674

2232

2790

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.376

Hom.:

14435

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

(source)

DANN

Benign

0.73

PhyloP100

-1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over