Genetic Variant TYRP1:c.914-374A>T (chr9-12701897-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.95

Publications

3 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

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.914-374A>T		intron	N/A	NP_000541.1	P17643
	LURAP1L-AS1	NR_125775.1		n.317-1271T>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TYRP1	ENST00000388918.10	TSL:1 MANE Select	c.914-374A>T	intron	N/A	ENSP00000373570.4	P17643
TYRP1	ENST00000381136.2	TSL:2	c.44-374A>T	intron	N/A	ENSP00000370528.2	E7EQI3
TYRP1	ENST00000381142.3	TSL:2	n.151-374A>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.505

AC:

76547

AN:

151626

Hom.:

22577

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.290

AC:

180

AN:

620

American (AMR)

AF:

0.472

AC:

1510

AN:

3202

Ashkenazi Jewish (ASJ)

AF:

0.558

AC:

513

AN:

920

East Asian (EAS)

AF:

0.0157

AC:

AN:

2096

South Asian (SAS)

AF:

0.255

AC:

1402

AN:

5508

European-Finnish (FIN)

AF:

0.724

AC:

1217

AN:

1682

Middle Eastern (MID)

AF:

0.492

AC:

AN:

130

European-Non Finnish (NFE)

AF:

0.685

AC:

17042

AN:

24864

Other (OTH)

AF:

0.600

AC:

1322

AN:

2202

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

401

803

1204

1606

2007

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

256

384

512

640

<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:

0.505

AC:

76597

AN:

151746

Hom.:

22589

Cov.:

AF XY:

0.497

AC XY:

36825

AN XY:

74138

show subpopulations

African (AFR)

AF:

0.279

AC:

11557

AN:

41418

American (AMR)

AF:

0.435

AC:

6620

AN:

15206

Ashkenazi Jewish (ASJ)

AF:

0.558

AC:

1936

AN:

3470

East Asian (EAS)

AF:

0.0204

AC:

105

AN:

5156

South Asian (SAS)

AF:

0.237

AC:

1142

AN:

4826

European-Finnish (FIN)

AF:

0.716

AC:

7506

AN:

10476

Middle Eastern (MID)

AF:

0.459

AC:

134

AN:

292

European-Non Finnish (NFE)

AF:

0.679

AC:

46059

AN:

67882

Other (OTH)

AF:

0.503

AC:

1062

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1592

3184

4775

6367

7959

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

644

1288

1932

2576

3220

<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:

0.491

Hom.:

1683

Bravo

AF:

0.479

Asia WGS

AF:

0.154

AC:

538

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.0010

(source)

DANN

Benign

0.47

PhyloP100

-6.0

Mutation Taster

=100/0

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

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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