rs4778211

Variant names:

• chr15-27954159-A-C
• rs4778211
• NM_000275.3:c.1842+999T>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000275.3(OCA2):​c.1842+999T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.031 (40 hom., cov: 0)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.85

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=-1.0).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0309 (1703/55060) while in subpopulation AFR AF= 0.0468 (1309/28000). AF 95% confidence interval is 0.0446. There are 40 homozygotes in gnomad4. There are 834 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 40 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OCA2	NM_000275.3	c.1842+999T>G		intron_variant	Intron 17 of 23	ENST00000354638.8	NP_000266.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OCA2	ENST00000354638.8	c.1842+999T>G		intron_variant	Intron 17 of 23	1	NM_000275.3	ENSP00000346659.3
OCA2	ENST00000353809.9	c.1770+999T>G		intron_variant	Intron 16 of 22	1		ENSP00000261276.8

Frequencies

GnomAD3 genomes AF: 0.0309 AC: 1696 AN: 54942 Hom.: 40 Cov.: 0

Gnomad AFR AF: 0.0467

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0214

Gnomad ASJ AF: 0.00648

Gnomad EAS AF: 0.0137

Gnomad SAS AF: 0.0149

Gnomad FIN AF: 0.00341

Gnomad MID AF: 0.0227

Gnomad NFE AF: 0.0135

Gnomad OTH AF: 0.0179

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

GnomAD4 genome AF: 0.0309 AC: 1703 AN: 55060 Hom.: 40 Cov.: 0 AF XY: 0.0309 AC XY: 834 AN XY: 27000

Gnomad4 AFR AF: 0.0467

Gnomad4 AMR AF: 0.0213

Gnomad4 ASJ AF: 0.00648

Gnomad4 EAS AF: 0.0138

Gnomad4 SAS AF: 0.0149

Gnomad4 FIN AF: 0.00341

Gnomad4 NFE AF: 0.0135

Gnomad4 OTH AF: 0.0175

Alfa AF: 0.816 Hom.: 54096

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.62
DANN	Benign	0.39

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: rs4778211; hg19: chr15-28199305; COSMIC: COSV62349879;