rs4778241

Variant names:

• chr15-28093567-A-C
• rs4778241
• NM_000275.3:c.-22+5657T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000275.3(OCA2):​c.-22+5657T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.678 in 151,978 control chromosomes in the GnomAD database, including 37,383 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as no classification for the single variant (no stars).

• Frequency: Genomes: 𝑓 0.68 (37383 hom., cov: 32)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.300
• Publications: 32 publications found

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]

OCA2 Gene-Disease associations (from GenCC):

• oculocutaneous albinism type 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.82 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000275.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OCA2	NM_000275.3	MANE Select	c.-22+5657T>G		intron	N/A	NP_000266.2	Q04671-1
	OCA2	NM_001300984.2		c.-22+5657T>G		intron	N/A	NP_001287913.1	Q04671-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OCA2	ENST00000354638.8	TSL:1 MANE Select	c.-22+5657T>G		intron	N/A	ENSP00000346659.3	Q04671-1
	OCA2	ENST00000353809.9	TSL:1	c.-22+5657T>G		intron	N/A	ENSP00000261276.8	Q04671-2
	OCA2	ENST00000910120.1		c.-22+5657T>G		intron	N/A	ENSP00000580179.1

Frequencies

GnomAD3 genomes AF: 0.679 AC: 103066 AN: 151860 Hom.: 37385 Cov.: 32

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.743

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.734

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.861

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.826

Gnomad OTH AF: 0.647

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

GnomAD4 genome AF: 0.678 AC: 103100 AN: 151978 Hom.: 37383 Cov.: 32 AF XY: 0.669 AC XY: 49691 AN XY: 74282

African (AFR) AF: 0.496 AC: 20553 AN: 41424

American (AMR) AF: 0.598 AC: 9141 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.734 AC: 2547 AN: 3472

East Asian (EAS) AF: 0.221 AC: 1140 AN: 5170

South Asian (SAS) AF: 0.480 AC: 2314 AN: 4818

European-Finnish (FIN) AF: 0.861 AC: 9069 AN: 10532

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.826 AC: 56129 AN: 67978

Other (OTH) AF: 0.645 AC: 1358 AN: 2106

Alfa AF: 0.758 Hom.: 73306

Bravo AF: 0.652

Asia WGS AF: 0.405 AC: 1412 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	11
DANN	Benign	0.78
PhyloP100		0.30
Mutation Taster		=21/79	disease causing (long InDel)

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

Other links and lift over

dbSNP: rs4778241; hg19: chr15-28338713;