rs7171246

chr15-27789763-C-T

Variant summary

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

The NM_000275.3(OCA2):c.2433-34291G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 151,970 control chromosomes in the GnomAD database, including 6,901 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 0.28 (6901 hom., cov: 33)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.429

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OCA2	NM_000275.3	c.2433-34291G>A		intron_variant		ENST00000354638.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OCA2	ENST00000354638.8	c.2433-34291G>A		intron_variant		1	NM_000275.3	P1
OCA2	ENST00000353809.9	c.2361-34291G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42096 AN: 151852 Hom.: 6898 Cov.: 33

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.277 AC: 42118 AN: 151970 Hom.: 6901 Cov.: 33 AF XY: 0.271 AC XY: 20094 AN XY: 74264

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.252

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.419

Gnomad4 NFE AF: 0.369

Gnomad4 OTH AF: 0.223

Alfa AF: 0.339 Hom.: 1181

Bravo AF: 0.260

Asia WGS AF: 0.0640 AC: 221 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	2.5
Dann	Benign	0.60

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: rs7171246; hg19: chr15-28034909; COSMIC: COSV62340626;