rs683

Variant names:

• chr9-12709305-C-A
• rs683
• NM_000550.3:c.*123C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-12709305-C-A
• chr9-12709305-C-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 56 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
TYRP1	NM_000550.3	c.*123C>A		3_prime_UTR_variant	Exon 8 of 8	ENST00000388918.10	NP_000541.1
LURAP1L-AS1	NR_125775.1	n.317-8679G>T		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TYRP1	ENST00000388918.10	c.*123C>A		3_prime_UTR_variant	Exon 8 of 8	1	NM_000550.3	ENSP00000373570.4

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

African (AFR) AF: 0.183 AC: 3829 AN: 20908

American (AMR) AF: 0.426 AC: 16059 AN: 37702

Ashkenazi Jewish (ASJ) AF: 0.556 AC: 12004 AN: 21574

East Asian (EAS) AF: 0.00391 AC: 134 AN: 34236

South Asian (SAS) AF: 0.265 AC: 18570 AN: 70030

European-Finnish (FIN) AF: 0.703 AC: 26905 AN: 38248

Middle Eastern (MID) AF: 0.436 AC: 1461 AN: 3352

European-Non Finnish (NFE) AF: 0.660 AC: 406019 AN: 614956

Other (OTH) AF: 0.538 AC: 22063 AN: 41030

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

African (AFR) AF: 0.192 AC: 7962 AN: 41424

American (AMR) AF: 0.415 AC: 6308 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 1886 AN: 3470

East Asian (EAS) AF: 0.0113 AC: 58 AN: 5150

South Asian (SAS) AF: 0.231 AC: 1115 AN: 4824

European-Finnish (FIN) AF: 0.709 AC: 7496 AN: 10580

Middle Eastern (MID) AF: 0.432 AC: 126 AN: 292

European-Non Finnish (NFE) AF: 0.660 AC: 44781 AN: 67838

Other (OTH) AF: 0.469 AC: 986 AN: 2104

Alfa AF: 0.583 Hom.: 119797

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

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.67
DANN	Benign	0.29
PhyloP100		-0.37
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs683; hg19: chr9-12709305;