15-28042975-G-T

Position:

• chr15-28042975-G-T

Variant summary

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

The NM_000275.3(OCA2):​c.228-10812C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 152,032 control chromosomes in the GnomAD database, including 18,975 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 0.39 (18975 hom., cov: 32)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0900

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 (HGNC:):

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 = 0.866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OCA2	NM_000275.3	c.228-10812C>A		intron_variant		ENST00000354638.8	NP_000266.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OCA2	ENST00000354638.8	c.228-10812C>A		intron_variant		1	NM_000275.3	ENSP00000346659.3
OCA2	ENST00000353809.9	c.228-10812C>A		intron_variant		1		ENSP00000261276.8
OCA2	ENST00000431101.1	c.228-10812C>A		intron_variant		3		ENSP00000415431.1
OCA2	ENST00000445578.5	c.228-10812C>A		intron_variant		3		ENSP00000414425.1

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59356 AN: 151916 Hom.: 18928 Cov.: 32

Gnomad AFR AF: 0.832

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.887

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.391 AC: 59464 AN: 152032 Hom.: 18975 Cov.: 32 AF XY: 0.396 AC XY: 29412 AN XY: 74324

Gnomad4 AFR AF: 0.833

Gnomad4 AMR AF: 0.348

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.887

Gnomad4 SAS AF: 0.395

Gnomad4 FIN AF: 0.152

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.384

Alfa AF: 0.211 Hom.: 5450

Bravo AF: 0.425

Asia WGS AF: 0.622 AC: 2153 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.9
DANN	Benign	0.25

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: rs1470608; hg19: chr15-28288121;