NM_000275.3:c.228-8808G>C

Variant names:

• chr15-28040971-C-G
• rs7166228
• NM_000275.3:c.228-8808G>C

Variant summary

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

The NM_000275.3(OCA2):​c.228-8808G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0876 in 152,126 control chromosomes in the GnomAD database, including 1,631 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 0.088 (1631 hom., cov: 32)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OCA2	NM_000275.3	c.228-8808G>C		intron_variant	Intron 2 of 23	ENST00000354638.8	NP_000266.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OCA2	ENST00000354638.8	c.228-8808G>C		intron_variant	Intron 2 of 23	1	NM_000275.3	ENSP00000346659.3
OCA2	ENST00000353809.9	c.228-8808G>C		intron_variant	Intron 2 of 22	1		ENSP00000261276.8
OCA2	ENST00000431101.1	c.228-8808G>C		intron_variant	Intron 2 of 6	3		ENSP00000415431.1
OCA2	ENST00000445578.5	c.228-8808G>C		intron_variant	Intron 2 of 5	3		ENSP00000414425.1

Frequencies

GnomAD3 genomes AF: 0.0877 AC: 13332 AN: 152008 Hom.: 1631 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.0688

Gnomad ASJ AF: 0.0697

Gnomad EAS AF: 0.663

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.0290

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0348

Gnomad OTH AF: 0.0889

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

GnomAD4 genome AF: 0.0876 AC: 13328 AN: 152126 Hom.: 1631 Cov.: 32 AF XY: 0.0918 AC XY: 6830 AN XY: 74368

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.0686

Gnomad4 ASJ AF: 0.0697

Gnomad4 EAS AF: 0.663

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.0290

Gnomad4 NFE AF: 0.0347

Gnomad4 OTH AF: 0.0885

Alfa AF: 0.0499 Hom.: 46

Bravo AF: 0.0939

Asia WGS AF: 0.307 AC: 1067 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.7
DANN	Benign	0.47

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: rs7166228; hg19: chr15-28286117;