rs2762464

chr9-12709586-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000550.3(TYRP1):c.*404A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 184,574 control chromosomes in the GnomAD database, including 25,646 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.46 (20460 hom., cov: 32)
  • Exomes 𝑓: 0.51 (5186 hom.)
• Consequence: TYRP1 NM_000550.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.623

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 9-12709586-A-T is Benign according to our data. Variant chr9-12709586-A-T is described in ClinVar as [Benign]. Clinvar id is 364865.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TYRP1	NM_000550.3	c.*404A>T		3_prime_UTR_variant	8/8	ENST00000388918.10
LURAP1L-AS1	NR_125775.1	n.317-8960T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TYRP1	ENST00000388918.10	c.*404A>T		3_prime_UTR_variant	8/8	1	NM_000550.3	P1
LURAP1L-AS1	ENST00000417638.1	n.273-8960T>A		intron_variant, non_coding_transcript_variant		3
LURAP1L-AS1	ENST00000650458.1	n.193-10231T>A		intron_variant, non_coding_transcript_variant
LURAP1L-AS1	ENST00000654076.1	n.159-8960T>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69687 AN: 151660 Hom.: 20460 Cov.: 32

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.536

Gnomad EAS AF: 0.0112

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.709

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.663

Gnomad OTH AF: 0.465

GnomAD4 exome AF: 0.508 AC: 16657 AN: 32798 Hom.: 5186 Cov.: 0 AF XY: 0.483 AC XY: 8307 AN XY: 17208

Gnomad4 AFR exome AF: 0.116

Gnomad4 AMR exome AF: 0.439

Gnomad4 ASJ exome AF: 0.496

Gnomad4 EAS exome AF: 0.00718

Gnomad4 SAS exome AF: 0.240

Gnomad4 FIN exome AF: 0.710

Gnomad4 NFE exome AF: 0.660

Gnomad4 OTH exome AF: 0.564

GnomAD4 genome AF: 0.459 AC: 69686 AN: 151776 Hom.: 20460 Cov.: 32 AF XY: 0.453 AC XY: 33573 AN XY: 74184

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.408

Gnomad4 ASJ AF: 0.536

Gnomad4 EAS AF: 0.0111

Gnomad4 SAS AF: 0.232

Gnomad4 FIN AF: 0.709

Gnomad4 NFE AF: 0.663

Gnomad4 OTH AF: 0.461

Alfa AF: 0.561 Hom.: 3342

Bravo AF: 0.428

Asia WGS AF: 0.134 AC: 467 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Oculocutaneous albinism type 3 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	2.4
Dann	Benign	0.65

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: rs2762464; hg19: chr9-12709586; COSMIC: COSV66357980; COSMIC: COSV66357980;