rs4778220

Variant names:

• chr15-27975992-G-A
• rs4778220
• NM_000275.3:c.1503+7353C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-27975992-G-A
• chr15-27975992-G-C

Variant summary

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

The NM_000275.3(OCA2):​c.1503+7353C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.751 in 152,096 control chromosomes in the GnomAD database, including 44,086 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 0.75 (44086 hom., cov: 32)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.171
• Publications: 7 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: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P, ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OCA2	NM_000275.3	c.1503+7353C>T		intron_variant	Intron 14 of 23	ENST00000354638.8	NP_000266.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OCA2	ENST00000354638.8	c.1503+7353C>T		intron_variant	Intron 14 of 23	1	NM_000275.3	ENSP00000346659.3
OCA2	ENST00000353809.9	c.1431+7353C>T		intron_variant	Intron 13 of 22	1		ENSP00000261276.8

Frequencies

GnomAD3 genomes AF: 0.751 AC: 114102 AN: 151978 Hom.: 44075 Cov.: 32

Gnomad AFR AF: 0.571

Gnomad AMI AF: 0.874

Gnomad AMR AF: 0.713

Gnomad ASJ AF: 0.820

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.634

Gnomad FIN AF: 0.872

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.834

Gnomad OTH AF: 0.750

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

GnomAD4 genome AF: 0.751 AC: 114154 AN: 152096 Hom.: 44086 Cov.: 32 AF XY: 0.752 AC XY: 55902 AN XY: 74366

African (AFR) AF: 0.571 AC: 23667 AN: 41466

American (AMR) AF: 0.713 AC: 10881 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.820 AC: 2844 AN: 3470

East Asian (EAS) AF: 0.997 AC: 5169 AN: 5184

South Asian (SAS) AF: 0.634 AC: 3046 AN: 4808

European-Finnish (FIN) AF: 0.872 AC: 9237 AN: 10588

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.834 AC: 56707 AN: 67996

Other (OTH) AF: 0.747 AC: 1577 AN: 2110

Alfa AF: 0.805 Hom.: 29196

Bravo AF: 0.736

Asia WGS AF: 0.794 AC: 2756 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.3
DANN	Benign	0.40
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism (auto)

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: rs4778220; hg19: chr15-28221138;