dbSNP rs3212351: MC1R:c.-580-196_-580-195delAT (chr16-89917679-CAT-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The ENST00000570217.1(ENSG00000267048):n.202-196_202-195delAT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.38 ( 11664 hom., cov: 0)

Consequence

ENSG00000267048
ENST00000570217.1 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1O:1

Conservation

PhyloP100: 0.414

Publications

2 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:

LOC124903759 (HGNC:):

LOC124903759 links:

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new If you want to explore the variant's impact on the transcript ENST00000570217.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 16-89917679-CAT-C is Benign according to our data. Variant chr16-89917679-CAT-C is described in ClinVar as Benign. ClinVar VariationId is 1265010.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000570217.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MC1R	ENST00000555427.1	TSL:5	c.-580-196_-580-195delAT	intron	N/A	ENSP00000451760.1	G3V4F0
MC1R	ENST00000639847.1	TSL:5	c.-580-196_-580-195delAT	intron	N/A	ENSP00000492011.1	Q01726
ENSG00000267048	ENST00000570217.1	TSL:4	n.202-196_202-195delAT	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.384

AC:

58246

AN:

151830

Hom.:

11647

Cov.:

show subpopulations

Gnomad AFR

AF:

0.415

Gnomad AMI

AF:

0.291

Gnomad AMR

AF:

0.478

Gnomad ASJ

AF:

0.320

Gnomad EAS

AF:

0.647

Gnomad SAS

AF:

0.475

Gnomad FIN

AF:

0.435

Gnomad MID

AF:

0.522

Gnomad NFE

AF:

0.313

Gnomad OTH

AF:

0.380

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.384

AC:

58298

AN:

151948

Hom.:

11664

Cov.:

AF XY:

0.395

AC XY:

29293

AN XY:

74250

show subpopulations

African (AFR)

AF:

0.415

AC:

17204

AN:

41428

American (AMR)

AF:

0.478

AC:

7311

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.320

AC:

1108

AN:

3466

East Asian (EAS)

AF:

0.646

AC:

3327

AN:

5148

South Asian (SAS)

AF:

0.473

AC:

2285

AN:

4828

European-Finnish (FIN)

AF:

0.435

AC:

4580

AN:

10534

Middle Eastern (MID)

AF:

0.520

AC:

153

AN:

294

European-Non Finnish (NFE)

AF:

0.313

AC:

21258

AN:

67944

Other (OTH)

AF:

0.381

AC:

807

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1858

3717

5575

7434

9292

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

564

1128

1692

2256

2820

<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:

0.346

Hom.:

1142

Bravo

AF:

0.392

Asia WGS

AF:

0.518

AC:

1807

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Macular degeneration, age-related, neovascular type (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.41

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over