rs1448481

Variant names:

• chr15-28059841-T-C
• rs1448481
• NM_000275.3:c.227+21807A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

OCA2 Gene-Disease associations (from GenCC):

• oculocutaneous albinism type 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P, ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
OCA2	NM_000275.3	c.227+21807A>G		intron_variant	Intron 2 of 23	ENST00000354638.8	NP_000266.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OCA2	ENST00000354638.8	c.227+21807A>G		intron_variant	Intron 2 of 23	1	NM_000275.3	ENSP00000346659.3
OCA2	ENST00000353809.9	c.227+21807A>G		intron_variant	Intron 2 of 22	1		ENSP00000261276.8
OCA2	ENST00000431101.1	c.227+21807A>G		intron_variant	Intron 2 of 6	3		ENSP00000415431.1
OCA2	ENST00000445578.5	c.227+21807A>G		intron_variant	Intron 2 of 5	3		ENSP00000414425.1

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

African (AFR) AF: 0.419 AC: 17405 AN: 41492

American (AMR) AF: 0.0996 AC: 1524 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 546 AN: 3470

East Asian (EAS) AF: 0.0230 AC: 119 AN: 5174

South Asian (SAS) AF: 0.0806 AC: 389 AN: 4824

European-Finnish (FIN) AF: 0.0283 AC: 300 AN: 10610

Middle Eastern (MID) AF: 0.110 AC: 32 AN: 292

European-Non Finnish (NFE) AF: 0.0820 AC: 5578 AN: 68032

Other (OTH) AF: 0.147 AC: 310 AN: 2114

Alfa AF: 0.111 Hom.: 1107

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
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1448481; hg19: chr15-28304987;