rs10960756

Positions:

• chr9-12707206-G-A
• chr9-12707206-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000550.3(TYRP1):​c.1262-791G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0461 in 151,996 control chromosomes in the GnomAD database, including 955 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 0.046 (955 hom., cov: 32)
• Consequence: TYRP1 NM_000550.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.832

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TYRP1	NM_000550.3	c.1262-791G>A		intron_variant		ENST00000388918.10
LURAP1L-AS1	NR_125775.1	n.317-6580C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TYRP1	ENST00000388918.10	c.1262-791G>A		intron_variant		1	NM_000550.3	P1
LURAP1L-AS1	ENST00000417638.1	n.273-6580C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0461 AC: 6998 AN: 151878 Hom.: 951 Cov.: 32

Gnomad AFR AF: 0.00805

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.0158

Gnomad EAS AF: 0.504

Gnomad SAS AF: 0.0630

Gnomad FIN AF: 0.0310

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0120

Gnomad OTH AF: 0.0425

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

GnomAD4 genome AF: 0.0461 AC: 7011 AN: 151996 Hom.: 955 Cov.: 32 AF XY: 0.0525 AC XY: 3900 AN XY: 74280

Gnomad4 AFR AF: 0.00802

Gnomad4 AMR AF: 0.164

Gnomad4 ASJ AF: 0.0158

Gnomad4 EAS AF: 0.504

Gnomad4 SAS AF: 0.0627

Gnomad4 FIN AF: 0.0310

Gnomad4 NFE AF: 0.0120

Gnomad4 OTH AF: 0.0487

Alfa AF: 0.0273 Hom.: 361

Bravo AF: 0.0586

Asia WGS AF: 0.261 AC: 905 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.39
DANN	Benign	0.83

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: rs10960756; hg19: chr9-12707206;