chr9-12707206-G-A

Variant names:

• chr9-12707206-G-A
• rs10960756
• NM_000550.3:c.1262-791G>A

Variant summary

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

The NM_000550.3(TYRP1):​c.1262-791G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0461 in 151,996 control chromosomes in the GnomAD database, including 955 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 0.046 (955 hom., cov: 32)
• Consequence: TYRP1 NM_000550.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.832
• Publications: 4 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000550.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TYRP1	NM_000550.3	MANE Select	c.1262-791G>A		intron	N/A	NP_000541.1
	LURAP1L-AS1	NR_125775.1		n.317-6580C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TYRP1	ENST00000388918.10	TSL:1 MANE Select	c.1262-791G>A		intron	N/A	ENSP00000373570.4
	TYRP1	ENST00000381136.2	TSL:2	c.392-791G>A		intron	N/A	ENSP00000370528.2
	TYRP1	ENST00000381142.3	TSL:2	n.499-1771G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0461 AC: 6998 AN: 151878 Hom.: 951 Cov.: 32

Gnomad AFR AF: 0.00805

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.0158

Gnomad EAS AF: 0.504

Gnomad SAS AF: 0.0630

Gnomad FIN AF: 0.0310

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0120

Gnomad OTH AF: 0.0425

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

GnomAD4 genome AF: 0.0461 AC: 7011 AN: 151996 Hom.: 955 Cov.: 32 AF XY: 0.0525 AC XY: 3900 AN XY: 74280

African (AFR) AF: 0.00802 AC: 333 AN: 41500

American (AMR) AF: 0.164 AC: 2490 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.0158 AC: 55 AN: 3472

East Asian (EAS) AF: 0.504 AC: 2583 AN: 5128

South Asian (SAS) AF: 0.0627 AC: 302 AN: 4818

European-Finnish (FIN) AF: 0.0310 AC: 329 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0120 AC: 816 AN: 67940

Other (OTH) AF: 0.0487 AC: 103 AN: 2116

Alfa AF: 0.0302 Hom.: 1154

Bravo AF: 0.0586

Asia WGS AF: 0.261 AC: 905 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.39
DANN	Benign	0.83
PhyloP100		-0.83
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: rs10960756; hg19: chr9-12707206;