dbSNP rs2762464: TYRP1:c.*404A>T (chr9-12709586-A-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.*404A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 184,574 control chromosomes in the GnomAD database, including 25,646 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 20460 hom., cov: 32)

Exomes 𝑓: 0.51 ( 5186 hom. )

Consequence

TYRP1
NM_000550.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.623

Publications

11 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=-0.83).

BP6

Variant 9-12709586-A-T is Benign according to our data. Variant chr9-12709586-A-T is described in ClinVar as Benign. ClinVar VariationId is 364865.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.658 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.*404A>T		3_prime_UTR	Exon 8 of 8	NP_000541.1	P17643
	LURAP1L-AS1	NR_125775.1		n.317-8960T>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TYRP1	ENST00000388918.10	TSL:1 MANE Select	c.*404A>T	3_prime_UTR	Exon 8 of 8	ENSP00000373570.4	P17643
LURAP1L-AS1	ENST00000417638.1	TSL:3	n.273-8960T>A	intron	N/A
LURAP1L-AS1	ENST00000650458.1		n.193-10231T>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.459

AC:

69687

AN:

151660

Hom.:

20460

Cov.:

show subpopulations

Gnomad AFR

AF:

0.155

Gnomad AMI

AF:

0.525

Gnomad AMR

AF:

0.408

Gnomad ASJ

AF:

0.536

Gnomad EAS

AF:

0.0112

Gnomad SAS

AF:

0.232

Gnomad FIN

AF:

0.709

Gnomad MID

AF:

0.421

Gnomad NFE

AF:

0.663

Gnomad OTH

AF:

0.465

GnomAD4 exome

AF:

0.508

AC:

16657

AN:

32798

Hom.:

5186

Cov.:

AF XY:

0.483

AC XY:

8307

AN XY:

17208

show subpopulations

African (AFR)

AF:

0.116

AC:

119

AN:

1024

American (AMR)

AF:

0.439

AC:

1411

AN:

3216

Ashkenazi Jewish (ASJ)

AF:

0.496

AC:

397

AN:

800

East Asian (EAS)

AF:

0.00718

AC:

AN:

2784

South Asian (SAS)

AF:

0.240

AC:

960

AN:

3994

European-Finnish (FIN)

AF:

0.710

AC:

985

AN:

1388

Middle Eastern (MID)

AF:

0.478

AC:

AN:

European-Non Finnish (NFE)

AF:

0.660

AC:

11870

AN:

17992

Other (OTH)

AF:

0.564

AC:

851

AN:

1508

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

302

603

905

1206

1508

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

118

236

354

472

590

<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:

0.459

AC:

69686

AN:

151776

Hom.:

20460

Cov.:

AF XY:

0.453

AC XY:

33573

AN XY:

74184

show subpopulations

African (AFR)

AF:

0.155

AC:

6415

AN:

41474

American (AMR)

AF:

0.408

AC:

6208

AN:

15210

Ashkenazi Jewish (ASJ)

AF:

0.536

AC:

1856

AN:

3464

East Asian (EAS)

AF:

0.0111

AC:

AN:

5146

South Asian (SAS)

AF:

0.232

AC:

1121

AN:

4822

European-Finnish (FIN)

AF:

0.709

AC:

7491

AN:

10570

Middle Eastern (MID)

AF:

0.422

AC:

124

AN:

294

European-Non Finnish (NFE)

AF:

0.663

AC:

44964

AN:

67776

Other (OTH)

AF:

0.461

AC:

972

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1490

2980

4471

5961

7451

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

594

1188

1782

2376

2970

<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:

0.561

Hom.:

3342

Bravo

AF:

0.428

Asia WGS

AF:

0.134

AC:

467

AN:

3474

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Oculocutaneous albinism type 3 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.4

(source)

DANN

Benign

0.65

PhyloP100

0.62

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