rs1448484

Variant names:

• chr15-28038295-A-G
• rs1448484
• NM_000275.3:c.228-6132T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000275.3(OCA2):​c.228-6132T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,162 control chromosomes in the GnomAD database, including 10,238 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 0.20 (10238 hom., cov: 32)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0460
• Publications: 18 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: ClinGen, Orphanet, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000275.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OCA2	NM_000275.3	MANE Select	c.228-6132T>C		intron	N/A	NP_000266.2	Q04671-1
	OCA2	NM_001300984.2		c.228-6132T>C		intron	N/A	NP_001287913.1	Q04671-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OCA2	ENST00000354638.8	TSL:1 MANE Select	c.228-6132T>C		intron	N/A	ENSP00000346659.3	Q04671-1
	OCA2	ENST00000353809.9	TSL:1	c.228-6132T>C		intron	N/A	ENSP00000261276.8	Q04671-2
	OCA2	ENST00000910120.1		c.228-6132T>C		intron	N/A	ENSP00000580179.1

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30724 AN: 152044 Hom.: 10190 Cov.: 32

Gnomad AFR AF: 0.695

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0737

Gnomad ASJ AF: 0.0199

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0416

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.00423

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.203 AC: 30839 AN: 152162 Hom.: 10238 Cov.: 32 AF XY: 0.195 AC XY: 14533 AN XY: 74426

African (AFR) AF: 0.695 AC: 28811 AN: 41452

American (AMR) AF: 0.0736 AC: 1124 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0199 AC: 69 AN: 3468

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5174

South Asian (SAS) AF: 0.0412 AC: 199 AN: 4830

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10630

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.00423 AC: 288 AN: 68008

Other (OTH) AF: 0.153 AC: 324 AN: 2114

Alfa AF: 0.0781 Hom.: 7079

Asia WGS AF: 0.0950 AC: 331 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.7
DANN	Benign	0.65
PhyloP100		-0.046
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: rs1448484; hg19: chr15-28283441;