rs3212368
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_002386.4(MC1R):c.*12G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00795 in 1,602,696 control chromosomes in the GnomAD database, including 944 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.043 ( 499 hom., cov: 33)
Exomes 𝑓: 0.0043 ( 445 hom. )
Consequence
MC1R
NM_002386.4 3_prime_UTR
NM_002386.4 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.35
Genes affected
MC1R (HGNC:6929): (melanocortin 1 receptor) This intronless gene encodes the receptor protein for melanocyte-stimulating hormone (MSH). The encoded protein, a seven pass transmembrane G protein coupled receptor, controls melanogenesis. Two types of melanin exist: red pheomelanin and black eumelanin. Gene mutations that lead to a loss in function are associated with increased pheomelanin production, which leads to lighter skin and hair color. Eumelanin is photoprotective but pheomelanin may contribute to UV-induced skin damage by generating free radicals upon UV radiation. Binding of MSH to its receptor activates the receptor and stimulates eumelanin synthesis. This receptor is a major determining factor in sun sensitivity and is a genetic risk factor for melanoma and non-melanoma skin cancer. Over 30 variant alleles have been identified which correlate with skin and hair color, providing evidence that this gene is an important component in determining normal human pigment variation. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
Variant 16-89920224-G-A is Benign according to our data. Variant chr16-89920224-G-A is described in ClinVar as [Benign]. Clinvar id is 258650.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MC1R | NM_002386.4 | c.*12G>A | 3_prime_UTR_variant | 1/1 | ENST00000555147.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MC1R | ENST00000555147.2 | c.*12G>A | 3_prime_UTR_variant | 1/1 | NM_002386.4 | P1 | |||
ENST00000554623.1 | n.588C>T | non_coding_transcript_exon_variant | 2/2 | 3 | |||||
MC1R | ENST00000639847.1 | c.*12G>A | 3_prime_UTR_variant | 3/3 | 5 | P1 | |||
MC1R | ENST00000555427.1 | c.950+16G>A | intron_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.0429 AC: 6536AN: 152216Hom.: 497 Cov.: 33
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GnomAD3 exomes AF: 0.0110 AC: 2718AN: 246400Hom.: 190 AF XY: 0.00804 AC XY: 1076AN XY: 133888
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GnomAD4 exome AF: 0.00427 AC: 6196AN: 1450362Hom.: 445 Cov.: 32 AF XY: 0.00360 AC XY: 2601AN XY: 721830
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GnomAD4 genome AF: 0.0429 AC: 6541AN: 152334Hom.: 499 Cov.: 33 AF XY: 0.0413 AC XY: 3073AN XY: 74494
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Melanoma, cutaneous malignant, susceptibility to, 5 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 22, 2018 | - - |
Computational scores
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BayesDel_noAF
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DANN
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at