rs2733833

Variant names:

• chr9-12705095-T-G
• rs2733833
• NM_000550.3:c.1261+390T>G

Variant summary

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

The NM_000550.3(TYRP1):​c.1261+390T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 151,864 control chromosomes in the GnomAD database, including 21,748 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 0.49 (21748 hom., cov: 32)
• Consequence: TYRP1 NM_000550.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.159
• Publications: 3 publications found

Genes affected

TYRP1 (HGNC:12450): (tyrosinase related protein 1) This gene encodes a melanosomal enzyme that belongs to the tyrosinase family and plays an important role in the melanin biosynthetic pathway. Defects in this gene are the cause of rufous oculocutaneous albinism and oculocutaneous albinism type III. [provided by RefSeq, Mar 2009]

LURAP1L-AS1 (HGNC:49761): (LURAP1L antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TYRP1	NM_000550.3	c.1261+390T>G		intron_variant	Intron 6 of 7	ENST00000388918.10	NP_000541.1
LURAP1L-AS1	NR_125775.1	n.317-4469A>C		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TYRP1	ENST00000388918.10	c.1261+390T>G		intron_variant	Intron 6 of 7	1	NM_000550.3	ENSP00000373570.4

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73947 AN: 151748 Hom.: 21739 Cov.: 32

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.527

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.0205

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.718

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.673

Gnomad OTH AF: 0.492

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

GnomAD4 genome AF: 0.487 AC: 73988 AN: 151864 Hom.: 21748 Cov.: 32 AF XY: 0.480 AC XY: 35647 AN XY: 74226

African (AFR) AF: 0.228 AC: 9428 AN: 41430

American (AMR) AF: 0.427 AC: 6515 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.551 AC: 1910 AN: 3466

East Asian (EAS) AF: 0.0204 AC: 105 AN: 5152

South Asian (SAS) AF: 0.234 AC: 1129 AN: 4818

European-Finnish (FIN) AF: 0.718 AC: 7579 AN: 10554

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.673 AC: 45678 AN: 67890

Other (OTH) AF: 0.489 AC: 1029 AN: 2106

Alfa AF: 0.535 Hom.: 7922

Bravo AF: 0.458

Asia WGS AF: 0.152 AC: 529 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.73
DANN	Benign	0.55
PhyloP100		-0.16
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: rs2733833; hg19: chr9-12705095;