chr9-12693129-T-C

Variant names:

• chr9-12693129-T-C
• rs12001162
• ENST00000473763.1:c.-85-783T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000473763.1(TYRP1):​c.-85-783T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 152,250 control chromosomes in the GnomAD database, including 31 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 0.011 (31 hom., cov: 32)
• Consequence: TYRP1 ENST00000473763.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0980
• Publications: 0 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0107 (1633/152250) while in subpopulation AFR AF = 0.037 (1538/41534). AF 95% confidence interval is 0.0355. There are 31 homozygotes in GnomAd4. There are 759 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 31 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000473763.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TYRP1	ENST00000473763.1	TSL:4	c.-85-783T>C		intron	N/A	ENSP00000419006.1
	LURAP1L-AS1	ENST00000803542.1		n.310-61522A>G		intron	N/A
	LURAP1L-AS1	ENST00000803543.1		n.436-4579A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0107 AC: 1630 AN: 152132 Hom.: 31 Cov.: 32

Gnomad AFR AF: 0.0371

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00367

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.00574

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

GnomAD4 genome AF: 0.0107 AC: 1633 AN: 152250 Hom.: 31 Cov.: 32 AF XY: 0.0102 AC XY: 759 AN XY: 74454

African (AFR) AF: 0.0370 AC: 1538 AN: 41534

American (AMR) AF: 0.00366 AC: 56 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000338 AC: 23 AN: 68022

Other (OTH) AF: 0.00568 AC: 12 AN: 2112

Alfa AF: 0.00689 Hom.: 4

Bravo AF: 0.0125

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.7
DANN	Benign	0.83
PhyloP100		0.098
PromoterAI		0.0050	Neutral

Splicing

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

Other links and lift over

dbSNP: rs12001162; hg19: chr9-12693129;