rs4278697

chr15-27978226-A-G

Variant summary

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

The NM_000275.3(OCA2):c.1503+5119T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 152,062 control chromosomes in the GnomAD database, including 25,821 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 0.55 (25821 hom., cov: 32)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

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=-1.04).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.711 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OCA2	NM_000275.3	c.1503+5119T>C		intron_variant		ENST00000354638.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OCA2	ENST00000354638.8	c.1503+5119T>C		intron_variant		1	NM_000275.3	P1
OCA2	ENST00000353809.9	c.1431+5119T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83134 AN: 151942 Hom.: 25825 Cov.: 32

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.739

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.600

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.743

Gnomad MID AF: 0.650

Gnomad NFE AF: 0.717

Gnomad OTH AF: 0.542

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

GnomAD4 genome AF: 0.547 AC: 83145 AN: 152062 Hom.: 25821 Cov.: 32 AF XY: 0.541 AC XY: 40225 AN XY: 74336

Gnomad4 AFR AF: 0.319

Gnomad4 AMR AF: 0.445

Gnomad4 ASJ AF: 0.600

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.366

Gnomad4 FIN AF: 0.743

Gnomad4 NFE AF: 0.717

Gnomad4 OTH AF: 0.539

Alfa AF: 0.635 Hom.: 4098

Bravo AF: 0.517

Asia WGS AF: 0.308 AC: 1072 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.21
Dann	Benign	0.34

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: rs4278697; hg19: chr15-28223372;