rs3212367
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_002386.4(MC1R):c.900C>T(p.Phe300=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00317 in 1,614,052 control chromosomes in the GnomAD database, including 164 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.017 ( 92 hom., cov: 33)
Exomes 𝑓: 0.0017 ( 72 hom. )
Consequence
MC1R
NM_002386.4 synonymous
NM_002386.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.73
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 -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.35).
BP6
?
Variant 16-89920158-C-T is Benign according to our data. Variant chr16-89920158-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 258654.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=1.73 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0583 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MC1R | NM_002386.4 | c.900C>T | p.Phe300= | synonymous_variant | 1/1 | ENST00000555147.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MC1R | ENST00000555147.2 | c.900C>T | p.Phe300= | synonymous_variant | 1/1 | NM_002386.4 | P1 | ||
ENST00000554623.1 | n.654G>A | non_coding_transcript_exon_variant | 2/2 | 3 | |||||
MC1R | ENST00000555427.1 | c.900C>T | p.Phe300= | synonymous_variant | 3/4 | 5 | |||
MC1R | ENST00000639847.1 | c.900C>T | p.Phe300= | synonymous_variant | 3/3 | 5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0174 AC: 2646AN: 152254Hom.: 92 Cov.: 33
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GnomAD3 exomes AF: 0.00434 AC: 1082AN: 249048Hom.: 26 AF XY: 0.00328 AC XY: 444AN XY: 135200
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GnomAD4 exome AF: 0.00168 AC: 2462AN: 1461680Hom.: 72 Cov.: 34 AF XY: 0.00141 AC XY: 1023AN XY: 727126
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GnomAD4 genome ? AF: 0.0174 AC: 2652AN: 152372Hom.: 92 Cov.: 33 AF XY: 0.0171 AC XY: 1271AN XY: 74512
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Melanoma, cutaneous malignant, susceptibility to, 5 Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 28, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Oct 11, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 22, 2018 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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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