rs2228478
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_002386.4(MC1R):āc.942A>Gā(p.Thr314=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 1,613,248 control chromosomes in the GnomAD database, including 19,574 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.21 ( 4915 hom., cov: 33)
Exomes š: 0.13 ( 14659 hom. )
Consequence
MC1R
NM_002386.4 synonymous
NM_002386.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.194
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 -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
Variant 16-89920200-A-G is Benign according to our data. Variant chr16-89920200-A-G is described in ClinVar as [Benign]. Clinvar id is 258655.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.194 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MC1R | NM_002386.4 | c.942A>G | p.Thr314= | synonymous_variant | 1/1 | ENST00000555147.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MC1R | ENST00000555147.2 | c.942A>G | p.Thr314= | synonymous_variant | 1/1 | NM_002386.4 | P1 | ||
ENST00000554623.1 | n.612T>C | non_coding_transcript_exon_variant | 2/2 | 3 | |||||
MC1R | ENST00000555427.1 | c.942A>G | p.Thr314= | synonymous_variant | 3/4 | 5 | |||
MC1R | ENST00000639847.1 | c.942A>G | p.Thr314= | synonymous_variant | 3/3 | 5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.206 AC: 31298AN: 152080Hom.: 4896 Cov.: 33
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GnomAD3 exomes AF: 0.143 AC: 35535AN: 248648Hom.: 3789 AF XY: 0.140 AC XY: 18874AN XY: 135022
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GnomAD4 exome AF: 0.127 AC: 185131AN: 1461050Hom.: 14659 Cov.: 34 AF XY: 0.127 AC XY: 92463AN XY: 726836
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GnomAD4 genome AF: 0.206 AC: 31355AN: 152198Hom.: 4915 Cov.: 33 AF XY: 0.200 AC XY: 14879AN XY: 74434
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ClinVar
Significance: Benign
Submissions summary: Benign:4
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 | 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. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
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
Benign
CADD
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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