chr15-27947078-A-G

Position:

• chr15-27947078-A-G

Variant summary

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

The NM_000275.3(OCA2):​c.1951+4706T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 152,168 control chromosomes in the GnomAD database, including 24,725 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 0.51 (24725 hom., cov: 33)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OCA2	NM_000275.3	c.1951+4706T>C		intron_variant		ENST00000354638.8	NP_000266.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OCA2	ENST00000354638.8	c.1951+4706T>C		intron_variant		1	NM_000275.3	ENSP00000346659	P1
OCA2	ENST00000353809.9	c.1879+4706T>C		intron_variant		1		ENSP00000261276

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77912 AN: 152050 Hom.: 24734 Cov.: 33

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.749

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.599

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.727

Gnomad OTH AF: 0.525

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

GnomAD4 genome AF: 0.512 AC: 77895 AN: 152168 Hom.: 24725 Cov.: 33 AF XY: 0.505 AC XY: 37564 AN XY: 74404

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.437

Gnomad4 ASJ AF: 0.599

Gnomad4 EAS AF: 0.127

Gnomad4 SAS AF: 0.326

Gnomad4 FIN AF: 0.729

Gnomad4 NFE AF: 0.727

Gnomad4 OTH AF: 0.523

Alfa AF: 0.673 Hom.: 70123

Bravo AF: 0.480

Asia WGS AF: 0.270 AC: 942 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.6
DANN	Benign	0.57

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: rs7170451; hg19: chr15-28192224;