rs3212351

Positions:

• chr16-89917679-CAT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The XM_047435031.1(LOC124903759):​c.1041-196_1041-195del 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: LOC124903759 XM_047435031.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1 O:1
• Conservation: PhyloP100: 0.414

Genes affected

LOC124903759 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC124903759	XM_047435031.1	c.1041-196_1041-195del		intron_variant			XP_047290987.1
LOC124903759	XM_047435032.1	c.1041-147_1041-146del		intron_variant			XP_047290988.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MC1R	ENST00000555427.1	c.-580-196_-580-195del		intron_variant		5		ENSP00000451760
MC1R	ENST00000639847.1	c.-580-196_-580-195del		intron_variant		5		ENSP00000492011	P1

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58246 AN: 151830 Hom.: 11647 Cov.: 0

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.: 0 AF XY: 0.395 AC XY: 29293 AN XY: 74250

Gnomad4 AFR AF: 0.415

Gnomad4 AMR AF: 0.478

Gnomad4 ASJ AF: 0.320

Gnomad4 EAS AF: 0.646

Gnomad4 SAS AF: 0.473

Gnomad4 FIN AF: 0.435

Gnomad4 NFE AF: 0.313

Gnomad4 OTH AF: 0.381

Alfa AF: 0.346 Hom.: 1142

Bravo AF: 0.392

Asia WGS AF: 0.518 AC: 1807 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 10, 2019

- -

Macular degeneration, age-related, neovascular type Other:1

association, no assertion criteria provided

research

School of Pharmacy, University of Eastern Finland

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3212351; hg19: chr16-89984087;