rs1555623739
Variant names:
Variant summary
Our verdict is Benign. The variant received -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_002386.4(MC1R):c.120C>T(p.Ile40Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
MC1R
NM_002386.4 synonymous
NM_002386.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.210
Publications
0 publications found
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 was made for transcript
Our verdict: Benign. The variant received -11 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.68).
BP6
Variant 16-89919378-C-T is Benign according to our data. Variant chr16-89919378-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 470701.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.21 with no splicing effect.
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| MC1R | ENST00000555147.2 | c.120C>T | p.Ile40Ile | synonymous_variant | Exon 1 of 1 | 6 | NM_002386.4 | ENSP00000451605.1 | ||
| ENSG00000198211 | ENST00000556922.1 | c.120C>T | p.Ile40Ile | synonymous_variant | Exon 1 of 5 | 2 | ENSP00000451560.1 | |||
| MC1R | ENST00000555427.1 | c.120C>T | p.Ile40Ile | synonymous_variant | Exon 3 of 4 | 5 | ENSP00000451760.1 | |||
| MC1R | ENST00000639847.1 | c.120C>T | p.Ile40Ile | synonymous_variant | Exon 3 of 3 | 5 | ENSP00000492011.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1460984Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 726754 show subpopulations
GnomAD4 exome
AF:
AC:
4
AN:
1460984
Hom.:
Cov.:
30
AF XY:
AC XY:
1
AN XY:
726754
show subpopulations
African (AFR)
AF:
AC:
2
AN:
33480
American (AMR)
AF:
AC:
0
AN:
44718
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
AC:
0
AN:
52720
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
2
AN:
1111848
Other (OTH)
AF:
AC:
0
AN:
60356
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.513
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Melanoma, cutaneous malignant, susceptibility to, 5 Benign:1
Jan 23, 2017
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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