9-12701897-A-T

Variant summary

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

The NM_000550.3(TYRP1):c.914-374A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 192,970 control chromosomes in the GnomAD database, including 30,185 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 0.50 (22589 hom., cov: 31)
  • Exomes 𝑓: 0.56 (7596 hom.)
• Consequence: TYRP1 NM_000550.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.95

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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TYRP1	NM_000550.3	c.914-374A>T		intron_variant		ENST00000388918.10
LURAP1L-AS1	NR_125775.1	n.317-1271T>A		intron_variant, non_coding_transcript_variant
TYRP1	XM_047423841.1	c.709-374A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TYRP1	ENST00000388918.10	c.914-374A>T		intron_variant		1	NM_000550.3	P1
LURAP1L-AS1	ENST00000417638.1	n.273-1271T>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76547 AN: 151626 Hom.: 22577 Cov.: 31

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.0205

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.716

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.679

Gnomad OTH AF: 0.507

GnomAD4 exome AF: 0.565 AC: 23283 AN: 41224 Hom.: 7596 AF XY: 0.533 AC XY: 11489 AN XY: 21548

Gnomad4 AFR exome AF: 0.290

Gnomad4 AMR exome AF: 0.472

Gnomad4 ASJ exome AF: 0.558

Gnomad4 EAS exome AF: 0.0157

Gnomad4 SAS exome AF: 0.255

Gnomad4 FIN exome AF: 0.724

Gnomad4 NFE exome AF: 0.685

Gnomad4 OTH exome AF: 0.600

GnomAD4 genome AF: 0.505 AC: 76597 AN: 151746 Hom.: 22589 Cov.: 31 AF XY: 0.497 AC XY: 36825 AN XY: 74138

Gnomad4 AFR AF: 0.279

Gnomad4 AMR AF: 0.435

Gnomad4 ASJ AF: 0.558

Gnomad4 EAS AF: 0.0204

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.716

Gnomad4 NFE AF: 0.679

Gnomad4 OTH AF: 0.503

Alfa AF: 0.491 Hom.: 1683

Bravo AF: 0.479

Asia WGS AF: 0.154 AC: 538 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.0010
Dann	Benign	0.47

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: rs2762463; hg19: chr9-12701897;