rs910

Variant names:

• chr9-12710035-A-C
• rs910
• NM_000550.3:c.*853A>C

Your query was ambiguous. Multiple possible variants found:

• chr9-12710035-A-C
• chr9-12710035-A-G
• chr9-12710035-A-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.*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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.48
• Publications: 17 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=-0.98).
• BP6: Variant 9-12710035-A-C is Benign according to our data. Variant chr9-12710035-A-C is described in ClinVar as Benign. ClinVar VariationId is 364872.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TYRP1	NM_000550.3	c.*853A>C		3_prime_UTR_variant	Exon 8 of 8	ENST00000388918.10	NP_000541.1
LURAP1L-AS1	NR_125775.1	n.317-9409T>G		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TYRP1	ENST00000388918.10	c.*853A>C		3_prime_UTR_variant	Exon 8 of 8	1	NM_000550.3	ENSP00000373570.4

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.188 AC: 7790 AN: 41490

American (AMR) AF: 0.438 AC: 6654 AN: 15178

Ashkenazi Jewish (ASJ) AF: 0.547 AC: 1896 AN: 3464

East Asian (EAS) AF: 0.0204 AC: 105 AN: 5156

South Asian (SAS) AF: 0.237 AC: 1141 AN: 4824

European-Finnish (FIN) AF: 0.719 AC: 7607 AN: 10584

Middle Eastern (MID) AF: 0.473 AC: 138 AN: 292

European-Non Finnish (NFE) AF: 0.689 AC: 46680 AN: 67740

Other (OTH) AF: 0.498 AC: 1045 AN: 2100

Alfa AF: 0.596 Hom.: 35396

Bravo AF: 0.455

Asia WGS AF: 0.149 AC: 519 AN: 3468

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Oculocutaneous albinism type 3 Benign:1

Jan 13, 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	-0.98
CADD	Benign	0.23
DANN	Benign	0.77
PhyloP100		-3.5
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: rs910; hg19: chr9-12710035;