rs11631195

Positions:

• chr15-27776742-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.2433-21270C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 152,176 control chromosomes in the GnomAD database, including 6,819 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 0.27 (6806 hom., cov: 31)
  • Exomes 𝑓: 0.37 (13 hom.)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

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]

ENSG00000232394 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• 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	Protein	UniProt
OCA2	NM_000275.3	c.2433-21270C>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.2433-21270C>T		intron_variant		1	NM_000275.3	ENSP00000346659.3
OCA2	ENST00000353809.9	c.2361-21270C>T		intron_variant		1		ENSP00000261276.8
ENSG00000232394	ENST00000419100.1	n.362G>A		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41607 AN: 151892 Hom.: 6803 Cov.: 31

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.226

GnomAD4 exome AF: 0.367 AC: 61 AN: 166 Hom.: 13 Cov.: 0 AF XY: 0.347 AC XY: 43 AN XY: 124

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.417

Gnomad4 NFE exome AF: 0.396

Gnomad4 OTH exome AF: 0.375

GnomAD4 genome AF: 0.274 AC: 41627 AN: 152010 Hom.: 6806 Cov.: 31 AF XY: 0.267 AC XY: 19858 AN XY: 74260

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.00117

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.418

Gnomad4 NFE AF: 0.368

Gnomad4 OTH AF: 0.223

Alfa AF: 0.327 Hom.: 11446

Bravo AF: 0.256

Asia WGS AF: 0.0620 AC: 214 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.64
DANN	Benign	0.61

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: rs11631195; hg19: chr15-28021888;