rs3212353

Positions:

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

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_047435031.1(LOC124903759):​c.1041-141G>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: LOC124903759 XM_047435031.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.177

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC124903759	XM_047435031.1	c.1041-141G>A		intron_variant
LOC124903759	XM_047435032.1	c.1041-92G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MC1R	ENST00000555427.1	c.-580-141G>A		intron_variant		5
MC1R	ENST00000639847.1	c.-580-141G>A		intron_variant		5		P1

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

Gnomad4 AFR exome AF: 0.00928

Gnomad4 AMR exome AF: 0.00519

Gnomad4 ASJ exome AF: 0.00923

Gnomad4 EAS exome AF: 0.0145

Gnomad4 SAS exome AF: 0.0948

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00858

Gnomad4 OTH exome AF: 0.00823

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

Gnomad4 AFR AF: 0.00856

Gnomad4 AMR AF: 0.00517

Gnomad4 ASJ AF: 0.00778

Gnomad4 EAS AF: 0.00386

Gnomad4 SAS AF: 0.0759

Gnomad4 FIN AF: 0.00264

Gnomad4 NFE AF: 0.00722

Gnomad4 OTH AF: 0.00992

Alfa AF: 0.00775 Hom.: 7

Bravo AF: 0.00709

Asia WGS AF: 0.0330 AC: 114 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.6
DANN	Benign	0.57

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3212353; hg19: chr16-89984143;