rs1448481

chr15-28059841-T-C

Variant summary

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

The NM_000275.3(OCA2):c.227+21807A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,216 control chromosomes in the GnomAD database, including 4,036 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 0.17 (4036 hom., cov: 33)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OCA2	NM_000275.3	c.227+21807A>G		intron_variant		ENST00000354638.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OCA2	ENST00000354638.8	c.227+21807A>G		intron_variant		1	NM_000275.3	P1
OCA2	ENST00000353809.9	c.227+21807A>G		intron_variant		1
OCA2	ENST00000431101.1	c.227+21807A>G		intron_variant		3
OCA2	ENST00000445578.5	c.227+21807A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26192 AN: 152098 Hom.: 4028 Cov.: 33

Gnomad AFR AF: 0.420

Gnomad AMI AF: 0.0209

Gnomad AMR AF: 0.0998

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.0231

Gnomad SAS AF: 0.0802

Gnomad FIN AF: 0.0283

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0820

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.172 AC: 26222 AN: 152216 Hom.: 4036 Cov.: 33 AF XY: 0.165 AC XY: 12282 AN XY: 74428

Gnomad4 AFR AF: 0.419

Gnomad4 AMR AF: 0.0996

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.0230

Gnomad4 SAS AF: 0.0806

Gnomad4 FIN AF: 0.0283

Gnomad4 NFE AF: 0.0820

Gnomad4 OTH AF: 0.147

Alfa AF: 0.105 Hom.: 657

Bravo AF: 0.189

Asia WGS AF: 0.0830 AC: 291 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	0.32
Dann	Benign	0.27

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: rs1448481; hg19: chr15-28304987;