rs7174027

chr15-28083619-G-Achr15-28083619-G-Cchr15-28083619-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.-21-1724C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 152,142 control chromosomes in the GnomAD database, including 6,700 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 0.24 (6700 hom., cov: 33)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.973

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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OCA2	NM_000275.3	c.-21-1724C>T		intron_variant		ENST00000354638.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OCA2	ENST00000354638.8	c.-21-1724C>T		intron_variant		1	NM_000275.3	P1
OCA2	ENST00000353809.9	c.-21-1724C>T		intron_variant		1
OCA2	ENST00000431101.1	c.-21-1724C>T		intron_variant		3
OCA2	ENST00000445578.5	c.-21-1724C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36224 AN: 152024 Hom.: 6692 Cov.: 33

Gnomad AFR AF: 0.444

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.716

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.0578

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.260

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

GnomAD4 genome AF: 0.238 AC: 36277 AN: 152142 Hom.: 6700 Cov.: 33 AF XY: 0.243 AC XY: 18052 AN XY: 74410

Gnomad4 AFR AF: 0.444

Gnomad4 AMR AF: 0.219

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.717

Gnomad4 SAS AF: 0.359

Gnomad4 FIN AF: 0.0578

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.264

Alfa AF: 0.146 Hom.: 5027

Bravo AF: 0.260

Asia WGS AF: 0.485 AC: 1685 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.49
Dann	Benign	0.44

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: rs7174027; hg19: chr15-28328765;