rs1004611

chr15-27852132-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.2245-657C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 152,112 control chromosomes in the GnomAD database, including 9,956 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 0.36 (9956 hom., cov: 33)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OCA2	NM_000275.3	c.2245-657C>T		intron_variant		ENST00000354638.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OCA2	ENST00000354638.8	c.2245-657C>T		intron_variant		1	NM_000275.3	P1
OCA2	ENST00000353809.9	c.2173-657C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54293 AN: 151992 Hom.: 9956 Cov.: 33

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.545

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.445

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

GnomAD4 genome AF: 0.357 AC: 54317 AN: 152112 Hom.: 9956 Cov.: 33 AF XY: 0.355 AC XY: 26376 AN XY: 74346

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.384

Gnomad4 ASJ AF: 0.482

Gnomad4 EAS AF: 0.406

Gnomad4 SAS AF: 0.314

Gnomad4 FIN AF: 0.311

Gnomad4 NFE AF: 0.393

Gnomad4 OTH AF: 0.446

Alfa AF: 0.395 Hom.: 19088

Bravo AF: 0.363

Asia WGS AF: 0.322 AC: 1122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.070
Dann	Benign	0.75

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: rs1004611; hg19: chr15-28097278;