rs2075508

chr9-12698363-T-C

Variant summary

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

The NM_000550.3(TYRP1):c.709-88T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.097 in 1,297,354 control chromosomes in the GnomAD database, including 9,182 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 0.13 (1940 hom., cov: 32)
  • Exomes 𝑓: 0.092 (7242 hom.)
• Consequence: TYRP1 NM_000550.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.262

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TYRP1	NM_000550.3	c.709-88T>C		intron_variant		ENST00000388918.10
TYRP1	XM_047423841.1	c.708+2526T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TYRP1	ENST00000388918.10	c.709-88T>C		intron_variant		1	NM_000550.3	P1
TYRP1	ENST00000381136.2	c.43+2526T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20002 AN: 151976 Hom.: 1939 Cov.: 32

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0749

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.0237

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.0699

Gnomad OTH AF: 0.133

GnomAD4 exome AF: 0.0925 AC: 105892 AN: 1145260 Hom.: 7242 AF XY: 0.0983 AC XY: 57182 AN XY: 581900

Gnomad4 AFR exome AF: 0.269

Gnomad4 AMR exome AF: 0.0780

Gnomad4 ASJ exome AF: 0.0794

Gnomad4 EAS exome AF: 0.139

Gnomad4 SAS exome AF: 0.267

Gnomad4 FIN exome AF: 0.0310

Gnomad4 NFE exome AF: 0.0719

Gnomad4 OTH exome AF: 0.107

GnomAD4 genome AF: 0.132 AC: 20010 AN: 152094 Hom.: 1940 Cov.: 32 AF XY: 0.131 AC XY: 9710 AN XY: 74344

Gnomad4 AFR AF: 0.262

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.0749

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.272

Gnomad4 FIN AF: 0.0237

Gnomad4 NFE AF: 0.0699

Gnomad4 OTH AF: 0.133

Alfa AF: 0.0909 Hom.: 1160

Bravo AF: 0.141

Asia WGS AF: 0.162 AC: 561 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	2.6
Dann	Benign	0.66

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: rs2075508; hg19: chr9-12698363; COSMIC: COSV66358420; COSMIC: COSV66358420;