15-28038361-G-A

Position:

• chr15-28038361-G-A

Variant summary

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

The NM_000275.3(OCA2):​c.228-6198C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,132 control chromosomes in the GnomAD database, including 4,417 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 0.21 (4417 hom., cov: 33)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.602

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OCA2	NM_000275.3	c.228-6198C>T		intron_variant		ENST00000354638.8	NP_000266.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OCA2	ENST00000354638.8	c.228-6198C>T		intron_variant		1	NM_000275.3	ENSP00000346659.3
OCA2	ENST00000353809.9	c.228-6198C>T		intron_variant		1		ENSP00000261276.8
OCA2	ENST00000431101.1	c.228-6198C>T		intron_variant		3		ENSP00000415431.1
OCA2	ENST00000445578.5	c.228-6198C>T		intron_variant		3		ENSP00000414425.1

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31757 AN: 152014 Hom.: 4392 Cov.: 33

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.209 AC: 31833 AN: 152132 Hom.: 4417 Cov.: 33 AF XY: 0.214 AC XY: 15912 AN XY: 74384

Gnomad4 AFR AF: 0.384

Gnomad4 AMR AF: 0.248

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.215

Gnomad4 SAS AF: 0.252

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.107

Gnomad4 OTH AF: 0.232

Alfa AF: 0.132 Hom.: 3419

Bravo AF: 0.223

Asia WGS AF: 0.291 AC: 1008 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.70
DANN	Benign	0.50

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: rs16950821; hg19: chr15-28283507;