rs1973448

Positions:

• chr15-27863165-G-A
• chr15-27863165-G-C
• chr15-27863165-G-T

Variant summary

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

The NM_000275.3(OCA2):​c.2244+7989C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.785 in 152,042 control chromosomes in the GnomAD database, including 47,951 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 0.78 (47951 hom., cov: 31)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.826

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OCA2	NM_000275.3	c.2244+7989C>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.2244+7989C>T		intron_variant		1	NM_000275.3	ENSP00000346659.3
OCA2	ENST00000353809.9	c.2172+7989C>T		intron_variant		1		ENSP00000261276.8

Frequencies

GnomAD3 genomes AF: 0.785 AC: 119227 AN: 151924 Hom.: 47886 Cov.: 31

Gnomad AFR AF: 0.927

Gnomad AMI AF: 0.771

Gnomad AMR AF: 0.821

Gnomad ASJ AF: 0.849

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.892

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.681

Gnomad OTH AF: 0.838

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

GnomAD4 genome AF: 0.785 AC: 119352 AN: 152042 Hom.: 47951 Cov.: 31 AF XY: 0.789 AC XY: 58629 AN XY: 74306

Gnomad4 AFR AF: 0.927

Gnomad4 AMR AF: 0.821

Gnomad4 ASJ AF: 0.849

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.892

Gnomad4 FIN AF: 0.657

Gnomad4 NFE AF: 0.681

Gnomad4 OTH AF: 0.840

Alfa AF: 0.718 Hom.: 6858

Bravo AF: 0.804

Asia WGS AF: 0.949 AC: 3300 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.26
DANN	Benign	0.33

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: rs1973448; hg19: chr15-28108311;