rs12914687

Positions:

• chr15-27981395-C-T

Variant summary

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

The NM_000275.3(OCA2):​c.1503+1950G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 152,114 control chromosomes in the GnomAD database, including 24,260 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 0.51 (24260 hom., cov: 33)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.562

Genes affected

OCA2 (HGNC:8101): (OCA2 melanosomal transmembrane protein) This gene encodes the human homolog of the mouse p (pink-eyed dilution) gene. The encoded protein is believed to be an integral membrane protein involved in small molecule transport, specifically tyrosine, which is a precursor to melanin synthesis. It is involved in mammalian pigmentation, where it may control skin color variation and act as a determinant of brown or blue eye color. Mutations in this gene result in type 2 oculocutaneous albinism. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OCA2	NM_000275.3	c.1503+1950G>A		intron_variant		ENST00000354638.8	NP_000266.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OCA2	ENST00000354638.8	c.1503+1950G>A		intron_variant		1	NM_000275.3	ENSP00000346659	P1
OCA2	ENST00000353809.9	c.1431+1950G>A		intron_variant		1		ENSP00000261276

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77442 AN: 151996 Hom.: 24268 Cov.: 33

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.739

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.600

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.744

Gnomad MID AF: 0.634

Gnomad NFE AF: 0.715

Gnomad OTH AF: 0.516

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

GnomAD4 genome AF: 0.509 AC: 77429 AN: 152114 Hom.: 24260 Cov.: 33 AF XY: 0.504 AC XY: 37487 AN XY: 74354

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.432

Gnomad4 ASJ AF: 0.600

Gnomad4 EAS AF: 0.148

Gnomad4 SAS AF: 0.368

Gnomad4 FIN AF: 0.744

Gnomad4 NFE AF: 0.715

Gnomad4 OTH AF: 0.513

Alfa AF: 0.611 Hom.: 3970

Bravo AF: 0.475

Asia WGS AF: 0.305 AC: 1061 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.21
DANN	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs12914687; hg19: chr15-28226541;