rs4640131

Positions:

• chr15-28014717-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000275.3(OCA2):​c.1044+59T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0644 in 1,584,610 control chromosomes in the GnomAD database, including 5,111 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (1269 hom., cov: 32)
  • Exomes 𝑓: 0.060 (3842 hom.)
• Consequence: OCA2 NM_000275.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.375

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 15-28014717-A-G is Benign according to our data. Variant chr15-28014717-A-G is described in ClinVar as [Benign]. Clinvar id is 1285944.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OCA2	NM_000275.3	c.1044+59T>C		intron_variant		ENST00000354638.8	NP_000266.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OCA2	ENST00000354638.8	c.1044+59T>C		intron_variant		1	NM_000275.3	ENSP00000346659.3
OCA2	ENST00000353809.9	c.1044+59T>C		intron_variant		1		ENSP00000261276.8

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15374 AN: 152068 Hom.: 1249 Cov.: 32

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.0708

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.00829

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.0310

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0507

Gnomad OTH AF: 0.0947

GnomAD4 exome AF: 0.0605 AC: 86653 AN: 1432424 Hom.: 3842 AF XY: 0.0629 AC XY: 44823 AN XY: 712668

Gnomad4 AFR exome AF: 0.222

Gnomad4 AMR exome AF: 0.0422

Gnomad4 ASJ exome AF: 0.155

Gnomad4 EAS exome AF: 0.00458

Gnomad4 SAS exome AF: 0.141

Gnomad4 FIN exome AF: 0.0322

Gnomad4 NFE exome AF: 0.0499

Gnomad4 OTH exome AF: 0.0753

GnomAD4 genome AF: 0.101 AC: 15427 AN: 152186 Hom.: 1269 Cov.: 32 AF XY: 0.101 AC XY: 7543 AN XY: 74400

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.0706

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.00831

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.0310

Gnomad4 NFE AF: 0.0507

Gnomad4 OTH AF: 0.0938

Alfa AF: 0.0654 Hom.: 454

Bravo AF: 0.107

Asia WGS AF: 0.0980 AC: 340 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 20, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.27

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: rs4640131; hg19: chr15-28259863;