rs885479

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002386.4(MC1R):c.488G>A(p.Arg163Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0824 in 1,607,552 control chromosomes in the GnomAD database, including 19,024 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.091 ( 2038 hom., cov: 33)

Exomes 𝑓: 0.082 ( 16986 hom. )

Consequence

MC1R
NM_002386.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.07

Publications

263 publications found

Variant links:

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]

MC1R links:

ENSG00000198211 (HGNC:):

ENSG00000198211 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.213233E-5).

BP6

Variant 16-89919746-G-A is Benign according to our data. Variant chr16-89919746-G-A is described in ClinVar as Benign. ClinVar VariationId is 258652.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.62 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MC1R	NM_002386.4 link	c.488G>A	p.Arg163Gln	missense_variant	Exon 1 of 1	ENST00000555147.2	NP_002377.4	Q01726Q1JUL4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MC1R	ENST00000555147.2 link	c.488G>A	p.Arg163Gln	missense_variant	Exon 1 of 1	6	NM_002386.4	ENSP00000451605.1		Q01726
ENSG00000198211	ENST00000556922.1 link	c.488G>A	p.Arg163Gln	missense_variant	Exon 1 of 5	2		ENSP00000451560.1		A0A0B4J269

Frequencies

GnomAD3 genomes

AF:

0.0913

AC:

13896

AN:

152166

Hom.:

2038

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0172

Gnomad AMI

AF:

0.00440

Gnomad AMR

AF:

0.234

Gnomad ASJ

AF:

0.0334

Gnomad EAS

AF:

0.639

Gnomad SAS

AF:

0.0546

Gnomad FIN

AF:

0.231

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0486

Gnomad OTH

AF:

0.0788

GnomAD2 exomes

AF:

0.152

AC:

37008

AN:

244212

AF XY:

0.135

show subpopulations

Gnomad AFR exome

AF:

0.0166

Gnomad AMR exome

AF:

0.397

Gnomad ASJ exome

AF:

0.0344

Gnomad EAS exome

AF:

0.640

Gnomad FIN exome

AF:

0.227

Gnomad NFE exome

AF:

0.0482

Gnomad OTH exome

AF:

0.111

GnomAD4 exome

AF:

0.0815

AC:

118637

AN:

1455268

Hom.:

16986

Cov.:

AF XY:

0.0786

AC XY:

56958

AN XY:

724254

show subpopulations

African (AFR)

AF:

0.0125

AC:

418

AN:

33468

American (AMR)

AF:

0.377

AC:

16843

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.0342

AC:

892

AN:

26112

East Asian (EAS)

AF:

0.718

AC:

28515

AN:

39692

South Asian (SAS)

AF:

0.0436

AC:

3758

AN:

86244

European-Finnish (FIN)

AF:

0.213

AC:

10063

AN:

47184

Middle Eastern (MID)

AF:

0.0168

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0475

AC:

52835

AN:

1111782

Other (OTH)

AF:

0.0865

AC:

5216

AN:

60310

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

6113

12225

18338

24450

30563

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2386

4772

7158

9544

11930

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0913

AC:

13896

AN:

152284

Hom.:

2038

Cov.:

AF XY:

0.105

AC XY:

7844

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.0172

AC:

715

AN:

41578

American (AMR)

AF:

0.234

AC:

3584

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0334

AC:

116

AN:

3470

East Asian (EAS)

AF:

0.638

AC:

3291

AN:

5156

South Asian (SAS)

AF:

0.0542

AC:

262

AN:

4834

European-Finnish (FIN)

AF:

0.231

AC:

2453

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0486

AC:

3307

AN:

68012

Other (OTH)

AF:

0.0775

AC:

164

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

551

1102

1654

2205

2756

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

272

408

544

680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0657

Hom.:

2356

Bravo

AF:

0.0957

TwinsUK

AF:

0.0378

AC:

140

ALSPAC

AF:

0.0423

AC:

163

ESP6500AA

AF:

0.0153

AC:

ESP6500EA

AF:

0.0482

AC:

414

ExAC

AF:

0.134

AC:

16230

Asia WGS

AF:

0.293

AC:

1022

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Melanoma, cutaneous malignant, susceptibility to, 5

Benign:2

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 22, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 22547573, 30414346, 30531825, 29178624, 11487574, 21052032, 24335900, 22854540, 18366057, 17616515, 11875032, 23711066, 24660985, 23647022, 22464597) -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

Apr 14, 2022

Fulgent Genetics, Fulgent Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.083

.;T;T;.

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.77

T;.;T;T

MetaRNN

Benign

0.000032

T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.9

.;L;L;.

PhyloP100

1.1

PROVEAN

Benign

-0.42

N;.;N;N

REVEL

Benign

0.16

Sift

Benign

0.035

D;.;T;D

Sift4G

Benign

0.30

T;.;T;T

Polyphen

0.0040

.;B;B;.

Vest4

0.052

MPC

0.017

ClinPred

0.0049

GERP RS

4.8

Varity_R

0.10

gMVP

0.32

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over