9-12710473-T-G

Variant names:

• chr9-12710473-T-G
• rs41306079
• ENST00000417638.1:n.273-9847A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000417638.1(LURAP1L-AS1):​n.273-9847A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 151,320 control chromosomes in the GnomAD database, including 1,321 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.12 (1321 hom., cov: 31)
• Consequence: LURAP1L-AS1 ENST00000417638.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.632
• Publications: 0 publications found

Genes affected

LURAP1L-AS1 (HGNC:49761): (LURAP1L antisense RNA 1)

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]

TYRP1 Gene-Disease associations (from GenCC):

• oculocutaneous albinism type 3

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LURAP1L-AS1	NR_125775.1	n.317-9847A>C		intron_variant	Intron 3 of 3
TYRP1	NM_000550.3	c.*1291T>G		downstream_gene_variant		ENST00000388918.10	NP_000541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TYRP1	ENST00000388918.10	c.*1291T>G		downstream_gene_variant		1	NM_000550.3	ENSP00000373570.4

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18015 AN: 151206 Hom.: 1317 Cov.: 31

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.0945

Gnomad EAS AF: 0.0856

Gnomad SAS AF: 0.0764

Gnomad FIN AF: 0.0768

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.0854

Gnomad OTH AF: 0.113

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.119 AC: 18041 AN: 151320 Hom.: 1321 Cov.: 31 AF XY: 0.119 AC XY: 8768 AN XY: 73934

African (AFR) AF: 0.201 AC: 8314 AN: 41380

American (AMR) AF: 0.115 AC: 1731 AN: 15090

Ashkenazi Jewish (ASJ) AF: 0.0945 AC: 327 AN: 3462

East Asian (EAS) AF: 0.0858 AC: 441 AN: 5140

South Asian (SAS) AF: 0.0763 AC: 367 AN: 4810

European-Finnish (FIN) AF: 0.0768 AC: 813 AN: 10582

Middle Eastern (MID) AF: 0.0951 AC: 27 AN: 284

European-Non Finnish (NFE) AF: 0.0854 AC: 5771 AN: 67558

Other (OTH) AF: 0.112 AC: 235 AN: 2102

Alfa AF: 0.105 Hom.: 121

Bravo AF: 0.124

Asia WGS AF: 0.0860 AC: 295 AN: 3448

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	12
DANN	Benign	0.72
PhyloP100		0.63
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs41306079; hg19: chr9-12710473;