rs3212353

Variant names:

• chr16-89917735-G-A
• rs3212353
• ENST00000555427.1:c.-580-141G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-89917735-G-A
• chr16-89917735-G-C

Variant summary

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

The ENST00000570217.1(ENSG00000267048):​n.202-141G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00945 in 179,546 control chromosomes in the GnomAD database, including 27 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 0.0092 (26 hom., cov: 33)
  • Exomes 𝑓: 0.011 (1 hom.)
• Consequence: ENSG00000267048 ENST00000570217.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.177
• Publications: 1 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0695 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.-580-141G>A		intron	N/A	ENSP00000451760.1
	MC1R	ENST00000639847.1	TSL:5	c.-580-141G>A		intron	N/A	ENSP00000492011.1
	ENSG00000267048	ENST00000570217.1	TSL:4	n.202-141G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00921 AC: 1401 AN: 152190 Hom.: 26 Cov.: 33

Gnomad AFR AF: 0.00854

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.00517

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.00385

Gnomad SAS AF: 0.0756

Gnomad FIN AF: 0.00264

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.00722

Gnomad OTH AF: 0.0100

GnomAD4 exome AF: 0.0107 AC: 292 AN: 27238 Hom.: 1 AF XY: 0.0103 AC XY: 128 AN XY: 12486

African (AFR) AF: 0.00928 AC: 8 AN: 862

American (AMR) AF: 0.00519 AC: 3 AN: 578

Ashkenazi Jewish (ASJ) AF: 0.00923 AC: 16 AN: 1734

East Asian (EAS) AF: 0.0145 AC: 83 AN: 5722

South Asian (SAS) AF: 0.0948 AC: 22 AN: 232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20

Middle Eastern (MID) AF: 0.0407 AC: 7 AN: 172

European-Non Finnish (NFE) AF: 0.00858 AC: 135 AN: 15732

Other (OTH) AF: 0.00823 AC: 18 AN: 2186

GnomAD4 genome AF: 0.00922 AC: 1404 AN: 152308 Hom.: 26 Cov.: 33 AF XY: 0.00982 AC XY: 731 AN XY: 74466

African (AFR) AF: 0.00856 AC: 356 AN: 41578

American (AMR) AF: 0.00517 AC: 79 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00778 AC: 27 AN: 3472

East Asian (EAS) AF: 0.00386 AC: 20 AN: 5182

South Asian (SAS) AF: 0.0759 AC: 366 AN: 4824

European-Finnish (FIN) AF: 0.00264 AC: 28 AN: 10608

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.00722 AC: 491 AN: 68030

Other (OTH) AF: 0.00992 AC: 21 AN: 2116

Alfa AF: 0.00748 Hom.: 19

Bravo AF: 0.00709

Asia WGS AF: 0.0330 AC: 114 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.6
DANN	Benign	0.57
PhyloP100		-0.18
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: rs3212353; hg19: chr16-89984143;