NM_005912.3:c.*252A>G

Variant names:

• chr18-60371099-T-C
• rs6567166
• NM_005912.3:c.*252A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005912.3(MC4R):​c.*252A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 475,896 control chromosomes in the GnomAD database, including 172 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.025 (133 hom., cov: 32)
  • Exomes 𝑓: 0.0033 (39 hom.)
• Consequence: MC4R NM_005912.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0920
• Publications: 2 publications found

Genes affected

MC4R (HGNC:6932): (melanocortin 4 receptor) The protein encoded by this gene is a membrane-bound receptor and member of the melanocortin receptor family. The encoded protein interacts with adrenocorticotropic and MSH hormones and is mediated by G proteins. This is an intronless gene. Defects in this gene are a cause of autosomal dominant obesity. [provided by RefSeq, Jan 2010]

MC4R Gene-Disease associations (from GenCC):

• inherited obesity

  Inheritance: AD Classification: STRONG Submitted by: Laboratory for Molecular Medicine
• obesity due to melanocortin 4 receptor deficiency

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000285681 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 18-60371099-T-C is Benign according to our data. Variant chr18-60371099-T-C is described in ClinVar as Benign. ClinVar VariationId is 1175203.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0853 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005912.3. 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
	MC4R	NM_005912.3	MANE Select	c.*252A>G		3_prime_UTR	Exon 1 of 1	NP_005903.2	P32245

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MC4R	ENST00000299766.5	TSL:6 MANE Select	c.*252A>G		3_prime_UTR	Exon 1 of 1	ENSP00000299766.3	P32245
	ENSG00000285681	ENST00000650201.1		n.113+41754T>C		intron	N/A
	ENSG00000285681	ENST00000658928.1		n.156+41754T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0251 AC: 3813 AN: 152188 Hom.: 131 Cov.: 32

Gnomad AFR AF: 0.0874

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00942

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.0115

GnomAD4 exome AF: 0.00333 AC: 1077 AN: 323590 Hom.: 39 Cov.: 3 AF XY: 0.00282 AC XY: 486 AN XY: 172284

African (AFR) AF: 0.0865 AC: 839 AN: 9702

American (AMR) AF: 0.00536 AC: 76 AN: 14186

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9896

East Asian (EAS) AF: 0.00 AC: 0 AN: 20138

South Asian (SAS) AF: 0.000300 AC: 12 AN: 40036

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16588

Middle Eastern (MID) AF: 0.00151 AC: 2 AN: 1328

European-Non Finnish (NFE) AF: 0.000160 AC: 31 AN: 193240

Other (OTH) AF: 0.00633 AC: 117 AN: 18476

GnomAD4 genome AF: 0.0252 AC: 3836 AN: 152306 Hom.: 133 Cov.: 32 AF XY: 0.0248 AC XY: 1846 AN XY: 74482

African (AFR) AF: 0.0877 AC: 3643 AN: 41540

American (AMR) AF: 0.00941 AC: 144 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.0103 AC: 3 AN: 292

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 68040

Other (OTH) AF: 0.0114 AC: 24 AN: 2114

Alfa AF: 0.0102 Hom.: 70

Bravo AF: 0.0286

Asia WGS AF: 0.00780 AC: 27 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.5
DANN	Benign	0.39
PhyloP100		-0.092

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6567166; hg19: chr18-58038332;