18-60372527-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005912.3(MC4R):​c.-178A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000191 in 523,810 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
Exomes 𝑓: 0.0000019 ( 0 hom. )

Consequence

MC4R
NM_005912.3 5_prime_UTR_premature_start_codon_gain

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.138
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MC4RNM_005912.3 linkuse as main transcriptc.-178A>G 5_prime_UTR_premature_start_codon_gain_variant 1/1 ENST00000299766.5 NP_005903.2 P32245
MC4RNM_005912.3 linkuse as main transcriptc.-178A>G 5_prime_UTR_variant 1/1 ENST00000299766.5 NP_005903.2 P32245

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MC4RENST00000299766.5 linkuse as main transcriptc.-178A>G 5_prime_UTR_premature_start_codon_gain_variant 1/16 NM_005912.3 ENSP00000299766.3 P32245
MC4RENST00000299766.5 linkuse as main transcriptc.-178A>G 5_prime_UTR_variant 1/16 NM_005912.3 ENSP00000299766.3 P32245
ENSG00000285681ENST00000650201.1 linkuse as main transcriptn.113+43182T>C intron_variant
ENSG00000285681ENST00000658928.1 linkuse as main transcriptn.156+43182T>C intron_variant

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000191
AC:
1
AN:
523810
Hom.:
0
Cov.:
5
AF XY:
0.00000357
AC XY:
1
AN XY:
279726
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR 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:
0.00000328
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
CADD
Benign
5.3
DANN
Benign
0.75

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.

Other links and lift over

dbSNP: rs34114122; hg19: chr18-58039760; API