rs2209277

Variant names:

• chr9-12706236-T-C
• rs2209277
• NM_000550.3:c.1261+1531T>C

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+1531T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 151,916 control chromosomes in the GnomAD database, including 22,660 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 0.51 (22660 hom., cov: 32)
• Consequence: TYRP1 NM_000550.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TYRP1	NM_000550.3	c.1261+1531T>C		intron_variant	Intron 6 of 7	ENST00000388918.10	NP_000541.1
LURAP1L-AS1	NR_125775.1	n.317-5610A>G		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TYRP1	ENST00000388918.10	c.1261+1531T>C		intron_variant	Intron 6 of 7	1	NM_000550.3	ENSP00000373570.4

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76847 AN: 151800 Hom.: 22652 Cov.: 32

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.555

Gnomad EAS AF: 0.0202

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.718

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.678

Gnomad OTH AF: 0.507

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

GnomAD4 genome AF: 0.506 AC: 76892 AN: 151916 Hom.: 22660 Cov.: 32 AF XY: 0.498 AC XY: 36986 AN XY: 74248

African (AFR) AF: 0.285 AC: 11804 AN: 41482

American (AMR) AF: 0.434 AC: 6600 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 1924 AN: 3468

East Asian (EAS) AF: 0.0201 AC: 103 AN: 5132

South Asian (SAS) AF: 0.235 AC: 1133 AN: 4816

European-Finnish (FIN) AF: 0.718 AC: 7614 AN: 10598

Middle Eastern (MID) AF: 0.452 AC: 132 AN: 292

European-Non Finnish (NFE) AF: 0.678 AC: 46040 AN: 67890

Other (OTH) AF: 0.503 AC: 1064 AN: 2114

Alfa AF: 0.615 Hom.: 48108

Bravo AF: 0.480

Asia WGS AF: 0.155 AC: 542 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.1
DANN	Benign	0.52
PhyloP100		-1.2
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: rs2209277; hg19: chr9-12706236;