9-12707861-A-G

Variant names:

• chr9-12707861-A-G
• rs10809828
• NM_000550.3:c.1262-136A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000550.3. 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
	TYRP1	NM_000550.3	MANE Select	c.1262-136A>G		intron	N/A	NP_000541.1
	LURAP1L-AS1	NR_125775.1		n.317-7235T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TYRP1	ENST00000388918.10	TSL:1 MANE Select	c.1262-136A>G		intron	N/A	ENSP00000373570.4
	TYRP1	ENST00000473504.1	TSL:2	n.191A>G		non_coding_transcript_exon	Exon 1 of 2
	TYRP1	ENST00000381136.2	TSL:2	c.392-136A>G		intron	N/A	ENSP00000370528.2

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

African (AFR) AF: 0.494 AC: 7771 AN: 15738

American (AMR) AF: 0.464 AC: 8919 AN: 19210

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 4478 AN: 15150

East Asian (EAS) AF: 0.739 AC: 23435 AN: 31724

South Asian (SAS) AF: 0.333 AC: 14955 AN: 44970

European-Finnish (FIN) AF: 0.203 AC: 8394 AN: 41280

Middle Eastern (MID) AF: 0.370 AC: 874 AN: 2362

European-Non Finnish (NFE) AF: 0.231 AC: 102670 AN: 444328

Other (OTH) AF: 0.303 AC: 9739 AN: 32178

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

African (AFR) AF: 0.485 AC: 20096 AN: 41414

American (AMR) AF: 0.452 AC: 6873 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.308 AC: 1065 AN: 3462

East Asian (EAS) AF: 0.760 AC: 3891 AN: 5122

South Asian (SAS) AF: 0.340 AC: 1639 AN: 4814

European-Finnish (FIN) AF: 0.202 AC: 2132 AN: 10576

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.226 AC: 15354 AN: 67864

Other (OTH) AF: 0.359 AC: 756 AN: 2106

Alfa AF: 0.278 Hom.: 11695

Bravo AF: 0.368

Asia WGS AF: 0.544 AC: 1887 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.46
DANN	Benign	0.69
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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