9-12707861-A-G

Position:

• chr9-12707861-A-G

Variant summary

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

The NM_000550.3(TYRP1):​c.1262-136A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 798,700 control chromosomes in the GnomAD database, including 41,127 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 0.34 (10549 hom., cov: 32)
  • Exomes 𝑓: 0.28 (30578 hom.)
• Consequence: TYRP1 NM_000550.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.264

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TYRP1	NM_000550.3	c.1262-136A>G		intron_variant		ENST00000388918.10	NP_000541.1
LURAP1L-AS1	NR_125775.1	n.317-7235T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TYRP1	ENST00000388918.10	c.1262-136A>G		intron_variant		1	NM_000550.3	ENSP00000373570	P1
LURAP1L-AS1	ENST00000417638.1	n.273-7235T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52036 AN: 151642 Hom.: 10538 Cov.: 32

Gnomad AFR AF: 0.486

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.760

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.354

GnomAD4 exome AF: 0.280 AC: 181235 AN: 646940 Hom.: 30578 Cov.: 9 AF XY: 0.281 AC XY: 93907 AN XY: 334234

Gnomad4 AFR exome AF: 0.494

Gnomad4 AMR exome AF: 0.464

Gnomad4 ASJ exome AF: 0.296

Gnomad4 EAS exome AF: 0.739

Gnomad4 SAS exome AF: 0.333

Gnomad4 FIN exome AF: 0.203

Gnomad4 NFE exome AF: 0.231

Gnomad4 OTH exome AF: 0.303

GnomAD4 genome AF: 0.343 AC: 52086 AN: 151760 Hom.: 10549 Cov.: 32 AF XY: 0.346 AC XY: 25644 AN XY: 74148

Gnomad4 AFR AF: 0.485

Gnomad4 AMR AF: 0.452

Gnomad4 ASJ AF: 0.308

Gnomad4 EAS AF: 0.760

Gnomad4 SAS AF: 0.340

Gnomad4 FIN AF: 0.202

Gnomad4 NFE AF: 0.226

Gnomad4 OTH AF: 0.359

Alfa AF: 0.254 Hom.: 6867

Bravo AF: 0.368

Asia WGS AF: 0.544 AC: 1887 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.46
DANN	Benign	0.69

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: rs10809828; hg19: chr9-12707861; COSMIC: COSV66358422;