rs1375166

Positions:

• chr15-27888228-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.2080-16306G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 152,158 control chromosomes in the GnomAD database, including 3,926 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 0.19 (3926 hom., cov: 32)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.210

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OCA2	NM_000275.3	c.2080-16306G>A		intron_variant		ENST00000354638.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OCA2	ENST00000354638.8	c.2080-16306G>A		intron_variant		1	NM_000275.3	P1
OCA2	ENST00000353809.9	c.2008-16306G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28834 AN: 152040 Hom.: 3923 Cov.: 32

Gnomad AFR AF: 0.0421

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.190 AC: 28840 AN: 152158 Hom.: 3926 Cov.: 32 AF XY: 0.200 AC XY: 14842 AN XY: 74376

Gnomad4 AFR AF: 0.0420

Gnomad4 AMR AF: 0.327

Gnomad4 ASJ AF: 0.320

Gnomad4 EAS AF: 0.564

Gnomad4 SAS AF: 0.290

Gnomad4 FIN AF: 0.255

Gnomad4 NFE AF: 0.193

Gnomad4 OTH AF: 0.199

Alfa AF: 0.181 Hom.: 739

Bravo AF: 0.192

Asia WGS AF: 0.401 AC: 1394 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.2
DANN	Benign	0.38

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: rs1375166; hg19: chr15-28133374;