rs3212353
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The XM_047435031.1(LOC124903759):c.1041-141G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00945 in 179,546 control chromosomes in the GnomAD database, including 27 homozygotes. 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: 𝑓 0.0092 ( 26 hom., cov: 33)
Exomes 𝑓: 0.011 ( 1 hom. )
Consequence
LOC124903759
XM_047435031.1 intron
XM_047435031.1 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.177
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 -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0695 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LOC124903759 | XM_047435031.1 | c.1041-141G>A | intron_variant | ||||
LOC124903759 | XM_047435032.1 | c.1041-92G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MC1R | ENST00000555427.1 | c.-580-141G>A | intron_variant | 5 | |||||
MC1R | ENST00000639847.1 | c.-580-141G>A | intron_variant | 5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00921 AC: 1401AN: 152190Hom.: 26 Cov.: 33
GnomAD3 genomes
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GnomAD4 exome AF: 0.0107 AC: 292AN: 27238Hom.: 1 AF XY: 0.0103 AC XY: 128AN XY: 12486
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GnomAD4 genome ? AF: 0.00922 AC: 1404AN: 152308Hom.: 26 Cov.: 33 AF XY: 0.00982 AC XY: 731AN XY: 74466
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ClinVar
Not reported inComputational scores
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Name
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Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at