rs2228479
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_002386.4(MC1R):c.274G>A(p.Val92Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0851 in 1,612,832 control chromosomes in the GnomAD database, including 7,144 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V92L) has been classified as Benign.
Frequency
Consequence
NM_002386.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MC1R | NM_002386.4 | c.274G>A | p.Val92Met | missense_variant | 1/1 | ENST00000555147.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MC1R | ENST00000555147.2 | c.274G>A | p.Val92Met | missense_variant | 1/1 | NM_002386.4 | P1 | ||
MC1R | ENST00000555427.1 | c.274G>A | p.Val92Met | missense_variant | 3/4 | 5 | |||
MC1R | ENST00000639847.1 | c.274G>A | p.Val92Met | missense_variant | 3/3 | 5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0664 AC: 10102AN: 152194Hom.: 550 Cov.: 33
GnomAD3 exomes AF: 0.0781 AC: 19399AN: 248326Hom.: 1319 AF XY: 0.0762 AC XY: 10284AN XY: 134878
GnomAD4 exome AF: 0.0870 AC: 127110AN: 1460520Hom.: 6590 Cov.: 33 AF XY: 0.0852 AC XY: 61888AN XY: 726518
GnomAD4 genome ? AF: 0.0664 AC: 10108AN: 152312Hom.: 554 Cov.: 33 AF XY: 0.0647 AC XY: 4818AN XY: 74472
ClinVar
Submissions by phenotype
Melanoma, cutaneous malignant, susceptibility to, 5 Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 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 rule this variant out of causing disease. Therefore, this variant is classified as benign. - |
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 | Mar 01, 2019 | This variant is associated with the following publications: (PMID: 8990005, 17371441, 28555837, 22464597, 23647022, 24660985, 22854540, 22572819, 24335900, 19924138, 20876876, 24916031, 11487574, 18067130, 16463023, 7581459, 8944016, 12859622, 18366057, 17616515, 9302268, 26103569, 30531825, 31382929, 30414346, 28059796) - |
Skin/hair/eye pigmentation 2, red hair/fair skin Other:1
association, no assertion criteria provided | literature only | OMIM | Apr 01, 2006 | - - |
Skin/hair/eye pigmentation 2, blond hair/fair skin Other:1
association, no assertion criteria provided | literature only | OMIM | Apr 01, 2006 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at