Genetic Variant TYRP1:c.1261+20C>T (chr9-12704725-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000550.3(TYRP1):c.1261+20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 1,608,578 control chromosomes in the GnomAD database, including 243,064 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 16520 hom., cov: 32)

Exomes 𝑓: 0.54 ( 226544 hom. )

Consequence

TYRP1
NM_000550.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.07

Publications

28 publications found

Variant links:

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]

TYRP1 links:

LURAP1L-AS1 (HGNC:49761): (LURAP1L antisense RNA 1)

LURAP1L-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 9-12704725-C-T is Benign according to our data. Variant chr9-12704725-C-T is described in ClinVar as Benign. ClinVar VariationId is 256642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.593 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TYRP1	NM_000550.3	MANE Select	c.1261+20C>T		intron	N/A	NP_000541.1	P17643
	LURAP1L-AS1	NR_125775.1		n.317-4099G>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TYRP1	ENST00000388918.10	TSL:1 MANE Select	c.1261+20C>T	intron	N/A	ENSP00000373570.4	P17643
TYRP1	ENST00000381136.2	TSL:2	c.391+20C>T	intron	N/A	ENSP00000370528.2	E7EQI3
TYRP1	ENST00000381142.3	TSL:2	n.498+20C>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.411

AC:

62433

AN:

151736

Hom.:

16519

Cov.:

show subpopulations

Gnomad AFR

AF:

0.129

Gnomad AMI

AF:

0.454

Gnomad AMR

AF:

0.377

Gnomad ASJ

AF:

0.460

Gnomad EAS

AF:

0.0202

Gnomad SAS

AF:

0.218

Gnomad FIN

AF:

0.626

Gnomad MID

AF:

0.383

Gnomad NFE

AF:

0.598

Gnomad OTH

AF:

0.419

GnomAD2 exomes

AF:

0.447

AC:

111897

AN:

250122

AF XY:

0.448

show subpopulations

Gnomad AFR exome

AF:

0.122

Gnomad AMR exome

AF:

0.398

Gnomad ASJ exome

AF:

0.475

Gnomad EAS exome

AF:

0.0141

Gnomad FIN exome

AF:

0.629

Gnomad NFE exome

AF:

0.596

Gnomad OTH exome

AF:

0.486

GnomAD4 exome

AF:

0.537

AC:

782561

AN:

1456724

Hom.:

226544

Cov.:

AF XY:

0.530

AC XY:

384129

AN XY:

724996

show subpopulations

African (AFR)

AF:

0.111

AC:

3702

AN:

33340

American (AMR)

AF:

0.395

AC:

17632

AN:

44584

Ashkenazi Jewish (ASJ)

AF:

0.473

AC:

12315

AN:

26056

East Asian (EAS)

AF:

0.0211

AC:

838

AN:

39668

South Asian (SAS)

AF:

0.248

AC:

21388

AN:

86160

European-Finnish (FIN)

AF:

0.625

AC:

33031

AN:

52848

Middle Eastern (MID)

AF:

0.366

AC:

2104

AN:

5748

European-Non Finnish (NFE)

AF:

0.597

AC:

662089

AN:

1108120

Other (OTH)

AF:

0.489

AC:

29462

AN:

60200

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

15426

30851

46277

61702

77128

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17414

34828

52242

69656

87070

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.411

AC:

62437

AN:

151854

Hom.:

16520

Cov.:

AF XY:

0.405

AC XY:

30070

AN XY:

74214

show subpopulations

African (AFR)

AF:

0.129

AC:

5342

AN:

41442

American (AMR)

AF:

0.376

AC:

5731

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.460

AC:

1595

AN:

3466

East Asian (EAS)

AF:

0.0201

AC:

103

AN:

5134

South Asian (SAS)

AF:

0.219

AC:

1051

AN:

4810

European-Finnish (FIN)

AF:

0.626

AC:

6612

AN:

10568

Middle Eastern (MID)

AF:

0.381

AC:

112

AN:

294

European-Non Finnish (NFE)

AF:

0.598

AC:

40602

AN:

67890

Other (OTH)

AF:

0.416

AC:

877

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1542

3083

4625

6166

7708

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

552

1104

1656

2208

2760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.444

Hom.:

4543

Bravo

AF:

0.383

Asia WGS

AF:

0.134

AC:

467

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (1)

Oculocutaneous albinism type 3 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.8

(source)

DANN

Benign

0.48

PhyloP100

1.1

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over