18-60371099-T-C

Position:

• chr18-60371099-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MC4R	NM_005912.3	c.*252A>G		3_prime_UTR_variant	1/1	ENST00000299766.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MC4R	ENST00000299766.5	c.*252A>G		3_prime_UTR_variant	1/1		NM_005912.3	P1
	ENST00000658928.1	n.156+41754T>C		intron_variant, non_coding_transcript_variant
	ENST00000650201.1	n.113+41754T>C		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR exome AF: 0.0865

Gnomad4 AMR exome AF: 0.00536

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000300

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000160

Gnomad4 OTH exome AF: 0.00633

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

Gnomad4 AFR AF: 0.0877

Gnomad4 AMR AF: 0.00941

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000250

Gnomad4 OTH AF: 0.0114

Alfa AF: 0.00699 Hom.: 32

Bravo AF: 0.0286

Asia WGS AF: 0.00780 AC: 27 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6567166; hg19: chr18-58038332;