rs910

chr9-12710035-A-Cchr9-12710035-A-Gchr9-12710035-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.*853A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 151,738 control chromosomes in the GnomAD database, including 22,237 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.48 (22237 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: TYRP1 NM_000550.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.48

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=-0.98).
• BP6: Variant 9-12710035-A-C is Benign according to our data. Variant chr9-12710035-A-C is described in ClinVar as [Benign]. Clinvar id is 364872.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TYRP1	NM_000550.3	c.*853A>C		3_prime_UTR_variant	8/8	ENST00000388918.10
LURAP1L-AS1	NR_125775.1	n.317-9409T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TYRP1	ENST00000388918.10	c.*853A>C		3_prime_UTR_variant	8/8	1	NM_000550.3	P1
LURAP1L-AS1	ENST00000417638.1	n.273-9409T>G		intron_variant, non_coding_transcript_variant		3
LURAP1L-AS1	ENST00000650458.1	n.193-10680T>G		intron_variant, non_coding_transcript_variant
LURAP1L-AS1	ENST00000654076.1	n.159-9409T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73553 AN: 151620 Hom.: 22231 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.586

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.547

Gnomad EAS AF: 0.0205

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.719

Gnomad MID AF: 0.471

Gnomad NFE AF: 0.689

Gnomad OTH AF: 0.501

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.485 AC: 73589 AN: 151738 Hom.: 22237 Cov.: 32 AF XY: 0.477 AC XY: 35361 AN XY: 74156

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.438

Gnomad4 ASJ AF: 0.547

Gnomad4 EAS AF: 0.0204

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.719

Gnomad4 NFE AF: 0.689

Gnomad4 OTH AF: 0.498

Alfa AF: 0.615 Hom.: 27794

Bravo AF: 0.455

Asia WGS AF: 0.149 AC: 519 AN: 3468

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	-0.98
Cadd	Benign	0.23
Dann	Benign	0.77

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: rs910; hg19: chr9-12710035;