rs683

Positions:

• chr9-12709305-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000550.3(TYRP1):​c.*123C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 1,033,830 control chromosomes in the GnomAD database, including 181,164 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.47 (20688 hom., cov: 33)
  • Exomes 𝑓: 0.57 (160476 hom.)
• Consequence: TYRP1 NM_000550.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.369

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 9-12709305-C-A is Benign according to our data. Variant chr9-12709305-C-A is described in ClinVar as [Benign]. Clinvar id is 364861.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TYRP1	NM_000550.3	c.*123C>A		3_prime_UTR_variant	8/8	ENST00000388918.10	NP_000541.1
LURAP1L-AS1	NR_125775.1	n.317-8679G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TYRP1	ENST00000388918.10	c.*123C>A		3_prime_UTR_variant	8/8	1	NM_000550.3	ENSP00000373570	P1
LURAP1L-AS1	ENST00000417638.1	n.273-8679G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71166 AN: 151676 Hom.: 20681 Cov.: 33

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.0114

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.709

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.660

Gnomad OTH AF: 0.474

GnomAD4 exome AF: 0.575 AC: 507044 AN: 882036 Hom.: 160476 Cov.: 12 AF XY: 0.564 AC XY: 257913 AN XY: 457636

Gnomad4 AFR exome AF: 0.183

Gnomad4 AMR exome AF: 0.426

Gnomad4 ASJ exome AF: 0.556

Gnomad4 EAS exome AF: 0.00391

Gnomad4 SAS exome AF: 0.265

Gnomad4 FIN exome AF: 0.703

Gnomad4 NFE exome AF: 0.660

Gnomad4 OTH exome AF: 0.538

GnomAD4 genome AF: 0.469 AC: 71198 AN: 151794 Hom.: 20688 Cov.: 33 AF XY: 0.463 AC XY: 34330 AN XY: 74192

Gnomad4 AFR AF: 0.192

Gnomad4 AMR AF: 0.415

Gnomad4 ASJ AF: 0.544

Gnomad4 EAS AF: 0.0113

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.709

Gnomad4 NFE AF: 0.660

Gnomad4 OTH AF: 0.469

Alfa AF: 0.606 Hom.: 56505

Bravo AF: 0.439

Asia WGS AF: 0.138 AC: 482 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Oculocutaneous albinism type 3 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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. -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.67
DANN	Benign	0.29

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: rs683; hg19: chr9-12709305;