rs1805005
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM5BP4_StrongBP6_Very_StrongBA1
The NM_002386.4(MC1R):c.178G>T(p.Val60Leu) variant causes a missense change. The variant allele was found at a frequency of 0.106 in 1,613,224 control chromosomes in the GnomAD database, including 11,236 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V60?) has been classified as Pathogenic.
Frequency
Consequence
NM_002386.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MC1R | NM_002386.4 | c.178G>T | p.Val60Leu | missense_variant | 1/1 | ENST00000555147.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MC1R | ENST00000555147.2 | c.178G>T | p.Val60Leu | missense_variant | 1/1 | NM_002386.4 | P1 | ||
MC1R | ENST00000555427.1 | c.178G>T | p.Val60Leu | missense_variant | 3/4 | 5 | |||
MC1R | ENST00000639847.1 | c.178G>T | p.Val60Leu | missense_variant | 3/3 | 5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0803 AC: 12226AN: 152162Hom.: 782 Cov.: 33
GnomAD3 exomes AF: 0.0860 AC: 21392AN: 248798Hom.: 1467 AF XY: 0.0852 AC XY: 11518AN XY: 135146
GnomAD4 exome AF: 0.109 AC: 159401AN: 1460944Hom.: 10454 Cov.: 31 AF XY: 0.106 AC XY: 77330AN XY: 726744
GnomAD4 genome ? AF: 0.0803 AC: 12226AN: 152280Hom.: 782 Cov.: 33 AF XY: 0.0751 AC XY: 5589AN XY: 74458
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 | Feb 09, 2016 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 22, 2018 | This variant is associated with the following publications: (PMID: 22547573, 30414346, 31382929, 30531825, 27251790, 26103569, 9302268, 19077144, 20876876, 24335900, 18366057, 17616515, 11875032, 24660985, 24665948, 23647022, 10403794, 22464597) - |
Malignant tumor of breast Benign:1
Benign, no assertion criteria provided | clinical testing | Center of Medical Genetics and Primary Health Care | - | - - |
Tyrosinase-positive oculocutaneous albinism;C1849452:Skin/hair/eye pigmentation, variation in, 2;C2751295:Melanoma, cutaneous malignant, susceptibility to, 5;C2751296:Increased analgesia from kappa-opioid receptor agonist, female-specific Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Feb 21, 2022 | - - |
Skin/hair/eye pigmentation 2, blond hair/fair skin Other:1
association, no assertion criteria provided | literature only | OMIM | Oct 01, 1997 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at