15-28052887-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000275.3(OCA2):​c.228-20724C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,102 control chromosomes in the GnomAD database, including 7,272 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 ( 7272 hom., cov: 32)

Consequence

OCA2
NM_000275.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.140
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.96).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OCA2NM_000275.3 linkc.228-20724C>G intron_variant ENST00000354638.8 NP_000266.2 Q04671-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OCA2ENST00000354638.8 linkc.228-20724C>G intron_variant 1 NM_000275.3 ENSP00000346659.3 Q04671-1
OCA2ENST00000353809.9 linkc.228-20724C>G intron_variant 1 ENSP00000261276.8 Q04671-2
OCA2ENST00000431101.1 linkc.228-20724C>G intron_variant 3 ENSP00000415431.1 C9JDV3
OCA2ENST00000445578.5 linkc.228-20724C>G intron_variant 3 ENSP00000414425.1 C9JLG9

Frequencies

GnomAD3 genomes
AF:
0.243
AC:
36901
AN:
151984
Hom.:
7255
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.503
Gnomad AMI
AF:
0.0241
Gnomad AMR
AF:
0.189
Gnomad ASJ
AF:
0.213
Gnomad EAS
AF:
0.666
Gnomad SAS
AF:
0.183
Gnomad FIN
AF:
0.0511
Gnomad MID
AF:
0.193
Gnomad NFE
AF:
0.104
Gnomad OTH
AF:
0.228
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.243
AC:
36946
AN:
152102
Hom.:
7272
Cov.:
32
AF XY:
0.241
AC XY:
17938
AN XY:
74366
show subpopulations
Gnomad4 AFR
AF:
0.503
Gnomad4 AMR
AF:
0.189
Gnomad4 ASJ
AF:
0.213
Gnomad4 EAS
AF:
0.667
Gnomad4 SAS
AF:
0.182
Gnomad4 FIN
AF:
0.0511
Gnomad4 NFE
AF:
0.104
Gnomad4 OTH
AF:
0.226
Alfa
AF:
0.0431
Hom.:
38
Bravo
AF:
0.269
Asia WGS
AF:
0.364
AC:
1267
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.96
CADD
Benign
2.0
DANN
Benign
0.65

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs895828; hg19: chr15-28298033; API