rs17773630

Positions:

• chr18-60371227-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_005912.3(MC4R):​c.*124T>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 0.00676 in 1,008,936 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0049 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0071 (44 hom.)
• Consequence: MC4R NM_005912.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.49

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 18-60371227-A-G is Benign according to our data. Variant chr18-60371227-A-G is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00495 (754/152326) while in subpopulation SAS AF= 0.0153 (74/4828). AF 95% confidence interval is 0.0125. There are 4 homozygotes in gnomad4. There are 368 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 754 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MC4R	NM_005912.3	c.*124T>C		3_prime_UTR_variant	1/1	ENST00000299766.5	NP_005903.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MC4R	ENST00000299766.5	c.*124T>C		3_prime_UTR_variant	1/1		NM_005912.3	ENSP00000299766	P1
	ENST00000658928.1	n.156+41882A>G		intron_variant, non_coding_transcript_variant
	ENST00000650201.1	n.113+41882A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00496 AC: 755 AN: 152208 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00171

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.00196

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0153

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00808

Gnomad OTH AF: 0.00526

GnomAD4 exome AF: 0.00708 AC: 6062 AN: 856610 Hom.: 44 Cov.: 11 AF XY: 0.00752 AC XY: 3362 AN XY: 446922

Gnomad4 AFR exome AF: 0.00175

Gnomad4 AMR exome AF: 0.00236

Gnomad4 ASJ exome AF: 0.00115

Gnomad4 EAS exome AF: 0.0000545

Gnomad4 SAS exome AF: 0.0161

Gnomad4 FIN exome AF: 0.00123

Gnomad4 NFE exome AF: 0.00763

Gnomad4 OTH exome AF: 0.00588

GnomAD4 genome AF: 0.00495 AC: 754 AN: 152326 Hom.: 4 Cov.: 32 AF XY: 0.00494 AC XY: 368 AN XY: 74486

Gnomad4 AFR AF: 0.00171

Gnomad4 AMR AF: 0.00196

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0153

Gnomad4 FIN AF: 0.000471

Gnomad4 NFE AF: 0.00808

Gnomad4 OTH AF: 0.00521

Alfa AF: 0.00616 Hom.: 0

Bravo AF: 0.00458

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.6
DANN	Benign	0.65

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

Other links and lift over

dbSNP: rs17773630; hg19: chr18-58038460;