rs4778200

chr15-27862875-G-A

Variant summary

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

The NM_000275.3(OCA2):c.2244+8279C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 152,126 control chromosomes in the GnomAD database, including 5,105 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 0.23 (5105 hom., cov: 32)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.121

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 (EAS) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OCA2	NM_000275.3	c.2244+8279C>T		intron_variant		ENST00000354638.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OCA2	ENST00000354638.8	c.2244+8279C>T		intron_variant		1	NM_000275.3	P1
OCA2	ENST00000353809.9	c.2172+8279C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35466 AN: 152006 Hom.: 5098 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.561

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.233 AC: 35487 AN: 152126 Hom.: 5105 Cov.: 32 AF XY: 0.243 AC XY: 18034 AN XY: 74364

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.360

Gnomad4 ASJ AF: 0.348

Gnomad4 EAS AF: 0.561

Gnomad4 SAS AF: 0.352

Gnomad4 FIN AF: 0.282

Gnomad4 NFE AF: 0.231

Gnomad4 OTH AF: 0.250

Alfa AF: 0.243 Hom.: 1240

Bravo AF: 0.237

Asia WGS AF: 0.433 AC: 1506 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	2.4
Dann	Benign	0.59

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: rs4778200; hg19: chr15-28108021;