rs7495174

Positions:

• chr15-28099092-A-G
• chr15-28099092-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.-22+132T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 155,530 control chromosomes in the GnomAD database, including 2,284 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 0.13 (2198 hom., cov: 33)
  • Exomes 𝑓: 0.13 (86 hom.)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0940

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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OCA2	NM_000275.3	c.-22+132T>C		intron_variant		ENST00000354638.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OCA2	ENST00000354638.8	c.-22+132T>C		intron_variant		1	NM_000275.3	P1
OCA2	ENST00000353809.9	c.-22+132T>C		intron_variant		1
OCA2	ENST00000431101.1	c.-22+19T>C		intron_variant		3
OCA2	ENST00000445578.5	c.-22+132T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19234 AN: 152042 Hom.: 2200 Cov.: 33

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.656

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.0179

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.0667

Gnomad OTH AF: 0.154

GnomAD4 exome AF: 0.134 AC: 453 AN: 3370 Hom.: 86 Cov.: 0 AF XY: 0.129 AC XY: 238 AN XY: 1838

Gnomad4 AFR exome AF: 0.179

Gnomad4 AMR exome AF: 0.125

Gnomad4 ASJ exome AF: 0.0714

Gnomad4 EAS exome AF: 0.627

Gnomad4 SAS exome AF: 0.313

Gnomad4 FIN exome AF: 0.0231

Gnomad4 NFE exome AF: 0.0812

Gnomad4 OTH exome AF: 0.0915

GnomAD4 genome AF: 0.127 AC: 19253 AN: 152160 Hom.: 2198 Cov.: 33 AF XY: 0.132 AC XY: 9821 AN XY: 74378

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.166

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.656

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.0179

Gnomad4 NFE AF: 0.0667

Gnomad4 OTH AF: 0.152

Alfa AF: 0.0956 Hom.: 1654

Bravo AF: 0.142

Asia WGS AF: 0.365 AC: 1266 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.1
DANN	Benign	0.54

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: rs7495174; hg19: chr15-28344238;