NM_000275.3:c.227+15820T>C

Variant names:

• chr15-28065828-A-G
• rs7496968
• NM_000275.3:c.227+15820T>C

Variant summary

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

The NM_000275.3(OCA2):​c.227+15820T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 152,010 control chromosomes in the GnomAD database, including 7,399 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 0.25 (7399 hom., cov: 32)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34

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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OCA2	NM_000275.3	c.227+15820T>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.227+15820T>C		intron_variant	Intron 2 of 23	1	NM_000275.3	ENSP00000346659.3
OCA2	ENST00000353809.9	c.227+15820T>C		intron_variant	Intron 2 of 22	1		ENSP00000261276.8
OCA2	ENST00000431101.1	c.227+15820T>C		intron_variant	Intron 2 of 6	3		ENSP00000415431.1
OCA2	ENST00000445578.5	c.227+15820T>C		intron_variant	Intron 2 of 5	3		ENSP00000414425.1

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37846 AN: 151892 Hom.: 7384 Cov.: 32

Gnomad AFR AF: 0.506

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.666

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.0560

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.227

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

GnomAD4 genome AF: 0.249 AC: 37879 AN: 152010 Hom.: 7399 Cov.: 32 AF XY: 0.247 AC XY: 18377 AN XY: 74304

Gnomad4 AFR AF: 0.505

Gnomad4 AMR AF: 0.195

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.667

Gnomad4 SAS AF: 0.213

Gnomad4 FIN AF: 0.0560

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.224

Alfa AF: 0.147 Hom.: 1228

Bravo AF: 0.274

Asia WGS AF: 0.379 AC: 1319 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	0.53
DANN	Benign	0.52

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: rs7496968; hg19: chr15-28310974;