Genetic Variant NM_000550.3:c.709-88T>C (chr9-12698363-T-C) – 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.709-88T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.097 in 1,297,354 control chromosomes in the GnomAD database, including 9,182 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 0.13 ( 1940 hom., cov: 32)

Exomes 𝑓: 0.092 ( 7242 hom. )

Consequence

TYRP1
NM_000550.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.262

Publications

10 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.26 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.709-88T>C		intron	N/A	NP_000541.1	P17643

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TYRP1	ENST00000388918.10	TSL:1 MANE Select	c.709-88T>C	intron	N/A	ENSP00000373570.4	P17643
TYRP1	ENST00000381136.2	TSL:2	c.43+2526T>C	intron	N/A	ENSP00000370528.2	E7EQI3
LURAP1L-AS1	ENST00000803542.1		n.309+61189A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.132

AC:

20002

AN:

151976

Hom.:

1939

Cov.:

show subpopulations

Gnomad AFR

AF:

0.262

Gnomad AMI

AF:

0.113

Gnomad AMR

AF:

0.101

Gnomad ASJ

AF:

0.0749

Gnomad EAS

AF:

0.118

Gnomad SAS

AF:

0.273

Gnomad FIN

AF:

0.0237

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.0699

Gnomad OTH

AF:

0.133

GnomAD4 exome

AF:

0.0925

AC:

105892

AN:

1145260

Hom.:

7242

AF XY:

0.0983

AC XY:

57182

AN XY:

581900

show subpopulations

African (AFR)

AF:

0.269

AC:

7339

AN:

27312

American (AMR)

AF:

0.0780

AC:

3164

AN:

40570

Ashkenazi Jewish (ASJ)

AF:

0.0794

AC:

1894

AN:

23854

East Asian (EAS)

AF:

0.139

AC:

5212

AN:

37588

South Asian (SAS)

AF:

0.267

AC:

20609

AN:

77318

European-Finnish (FIN)

AF:

0.0310

AC:

1585

AN:

51196

Middle Eastern (MID)

AF:

0.181

AC:

936

AN:

5160

European-Non Finnish (NFE)

AF:

0.0719

AC:

59813

AN:

832398

Other (OTH)

AF:

0.107

AC:

5340

AN:

49864

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

5029

10059

15088

20118

25147

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2202

4404

6606

8808

11010

<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:

0.132

AC:

20010

AN:

152094

Hom.:

1940

Cov.:

AF XY:

0.131

AC XY:

9710

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.262

AC:

10852

AN:

41480

American (AMR)

AF:

0.101

AC:

1537

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.0749

AC:

260

AN:

3470

East Asian (EAS)

AF:

0.118

AC:

610

AN:

5170

South Asian (SAS)

AF:

0.272

AC:

1314

AN:

4824

European-Finnish (FIN)

AF:

0.0237

AC:

251

AN:

10596

Middle Eastern (MID)

AF:

0.170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0699

AC:

4753

AN:

67988

Other (OTH)

AF:

0.133

AC:

280

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

835

1670

2505

3340

4175

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

218

436

654

872

1090

<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:

0.0962

Hom.:

1808

Bravo

AF:

0.141

Asia WGS

AF:

0.162

AC:

561

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.6

(source)

DANN

Benign

0.66

PhyloP100

-0.26

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