rs4778214

Positions:

• chr15-27960418-A-G
• chr15-27960418-A-T

Variant summary

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

The NM_000275.3(OCA2):​c.1637-2683T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 152,088 control chromosomes in the GnomAD database, including 6,326 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 0.24 (6326 hom., cov: 32)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.109

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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OCA2	NM_000275.3	c.1637-2683T>C		intron_variant		ENST00000354638.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OCA2	ENST00000354638.8	c.1637-2683T>C		intron_variant		1	NM_000275.3	P1
OCA2	ENST00000353809.9	c.1565-2683T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36368 AN: 151968 Hom.: 6308 Cov.: 32

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.846

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.237

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

GnomAD4 genome AF: 0.240 AC: 36432 AN: 152088 Hom.: 6326 Cov.: 32 AF XY: 0.246 AC XY: 18292 AN XY: 74356

Gnomad4 AFR AF: 0.370

Gnomad4 AMR AF: 0.284

Gnomad4 ASJ AF: 0.222

Gnomad4 EAS AF: 0.846

Gnomad4 SAS AF: 0.293

Gnomad4 FIN AF: 0.128

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.237

Alfa AF: 0.150 Hom.: 2754

Bravo AF: 0.259

Asia WGS AF: 0.498 AC: 1728 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.8
DANN	Benign	0.52

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: rs4778214; hg19: chr15-28205564;