chr16-89915864-T-C

Variant names:

• chr16-89915864-T-C
• rs3212345
• ENST00000555427.1:c.-581+724T>C

Variant summary

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

The ENST00000570217.1(ENSG00000267048):​n.202-2012T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.594 in 152,280 control chromosomes in the GnomAD database, including 29,946 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 0.59 (29946 hom., cov: 35)
• Consequence: ENSG00000267048 ENST00000570217.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.264
• Publications: 8 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]

LOC124903759 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.895 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MC1R	ENST00000555427.1	TSL:5	c.-581+724T>C		intron	N/A	ENSP00000451760.1
	MC1R	ENST00000639847.1	TSL:5	c.-581+724T>C		intron	N/A	ENSP00000492011.1
	ENSG00000267048	ENST00000570217.1	TSL:4	n.202-2012T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.594 AC: 90388 AN: 152162 Hom.: 29890 Cov.: 35

Gnomad AFR AF: 0.865

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.587

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.917

Gnomad SAS AF: 0.680

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.548

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

GnomAD4 genome AF: 0.594 AC: 90504 AN: 152280 Hom.: 29946 Cov.: 35 AF XY: 0.599 AC XY: 44617 AN XY: 74454

African (AFR) AF: 0.865 AC: 35964 AN: 41564

American (AMR) AF: 0.587 AC: 8987 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 1388 AN: 3472

East Asian (EAS) AF: 0.917 AC: 4758 AN: 5190

South Asian (SAS) AF: 0.678 AC: 3276 AN: 4830

European-Finnish (FIN) AF: 0.518 AC: 5499 AN: 10614

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.426 AC: 28968 AN: 67990

Other (OTH) AF: 0.551 AC: 1165 AN: 2116

Alfa AF: 0.492 Hom.: 5376

Bravo AF: 0.611

Asia WGS AF: 0.774 AC: 2693 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.31
DANN	Benign	0.33
PhyloP100		-0.26
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs3212345; hg19: chr16-89982272;