rs3212346

Variant names:

• chr16-89915950-G-A
• rs3212346
• ENST00000555427.1:c.-581+810G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000555427.1(MC1R):​c.-581+810G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 152,236 control chromosomes in the GnomAD database, including 4,823 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.20 (4823 hom., cov: 33)
• Consequence: MC1R ENST00000555427.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0460
• Publications: 21 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]

ENSG00000267048 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124903759	XM_047435031.1	c.1040+810G>A		intron_variant	Intron 2 of 3		XP_047290987.1
LOC124903759	XM_047435032.1	c.1040+810G>A		intron_variant	Intron 2 of 2		XP_047290988.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MC1R	ENST00000555427.1	c.-581+810G>A		intron_variant	Intron 1 of 3	5		ENSP00000451760.1
MC1R	ENST00000639847.1	c.-581+810G>A		intron_variant	Intron 1 of 2	5		ENSP00000492011.1
ENSG00000267048	ENST00000570217.1	n.202-1926G>A		intron_variant	Intron 2 of 2	4

Frequencies

GnomAD3 genomes AF: 0.204 AC: 31070 AN: 152118 Hom.: 4803 Cov.: 33

Gnomad AFR AF: 0.434

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0839

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.0807

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.204 AC: 31128 AN: 152236 Hom.: 4823 Cov.: 33 AF XY: 0.198 AC XY: 14768 AN XY: 74442

African (AFR) AF: 0.434 AC: 18007 AN: 41522

American (AMR) AF: 0.105 AC: 1603 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0839 AC: 291 AN: 3470

East Asian (EAS) AF: 0.267 AC: 1378 AN: 5168

South Asian (SAS) AF: 0.201 AC: 970 AN: 4824

European-Finnish (FIN) AF: 0.0807 AC: 857 AN: 10616

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7599 AN: 68008

Other (OTH) AF: 0.163 AC: 344 AN: 2116

Alfa AF: 0.135 Hom.: 3332

Bravo AF: 0.213

Asia WGS AF: 0.252 AC: 875 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.3
DANN	Benign	0.60
PhyloP100		0.046
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs3212346; hg19: chr16-89982358;