rs2762462

chr9-12699776-T-Cchr9-12699776-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000550.3(TYRP1):c.913+1121T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.635 in 151,874 control chromosomes in the GnomAD database, including 32,113 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 0.63 (32113 hom., cov: 31)
• Consequence: TYRP1 NM_000550.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.31

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TYRP1	NM_000550.3	c.913+1121T>C		intron_variant		ENST00000388918.10
TYRP1	XM_047423841.1	c.709-2495T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TYRP1	ENST00000388918.10	c.913+1121T>C		intron_variant		1	NM_000550.3	P1
TYRP1	ENST00000381136.2	c.44-2495T>C		intron_variant		2
TYRP1	ENST00000381142.3	n.150+1121T>C		intron_variant, non_coding_transcript_variant		2
LURAP1L-AS1	ENST00000650458.1	n.193-421A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96346 AN: 151756 Hom.: 32098 Cov.: 31

Gnomad AFR AF: 0.540

Gnomad AMI AF: 0.641

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.741

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.747

Gnomad OTH AF: 0.635

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

GnomAD4 genome AF: 0.635 AC: 96397 AN: 151874 Hom.: 32113 Cov.: 31 AF XY: 0.627 AC XY: 46509 AN XY: 74236

Gnomad4 AFR AF: 0.540

Gnomad4 AMR AF: 0.533

Gnomad4 ASJ AF: 0.612

Gnomad4 EAS AF: 0.131

Gnomad4 SAS AF: 0.511

Gnomad4 FIN AF: 0.741

Gnomad4 NFE AF: 0.747

Gnomad4 OTH AF: 0.629

Alfa AF: 0.710 Hom.: 33042

Bravo AF: 0.616

Asia WGS AF: 0.309 AC: 1077 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.097
Dann	Benign	0.51

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: rs2762462; hg19: chr9-12699776;