rs41302073

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The ENST00000388918.10(TYRP1):ā€‹c.1557T>Gā€‹(p.Tyr519Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00196 in 1,612,736 control chromosomes in the GnomAD database, including 74 homozygotes. Variant has been reported in ClinVar as Likely benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.010 ( 36 hom., cov: 32)
Exomes š‘“: 0.0011 ( 38 hom. )

Consequence

TYRP1
ENST00000388918.10 stop_gained

Scores

1
4
2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 3.45
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]
LURAP1L-AS1 (HGNC:49761): (LURAP1L antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6
Variant 9-12709125-T-G is Benign according to our data. Variant chr9-12709125-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 198743.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0104 (1588/151986) while in subpopulation AFR AF= 0.0371 (1540/41492). AF 95% confidence interval is 0.0356. There are 36 homozygotes in gnomad4. There are 731 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 36 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TYRP1NM_000550.3 linkuse as main transcriptc.1557T>G p.Tyr519Ter stop_gained 8/8 ENST00000388918.10 NP_000541.1
LURAP1L-AS1NR_125775.1 linkuse as main transcriptn.317-8499A>C intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TYRP1ENST00000388918.10 linkuse as main transcriptc.1557T>G p.Tyr519Ter stop_gained 8/81 NM_000550.3 ENSP00000373570 P1
LURAP1L-AS1ENST00000417638.1 linkuse as main transcriptn.273-8499A>C intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.0105
AC:
1589
AN:
151868
Hom.:
36
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0372
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00217
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000442
Gnomad OTH
AF:
0.00574
GnomAD3 exomes
AF:
0.00267
AC:
670
AN:
250710
Hom.:
17
AF XY:
0.00184
AC XY:
249
AN XY:
135492
show subpopulations
Gnomad AFR exome
AF:
0.0398
Gnomad AMR exome
AF:
0.000493
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000883
Gnomad OTH exome
AF:
0.000654
GnomAD4 exome
AF:
0.00107
AC:
1569
AN:
1460750
Hom.:
38
Cov.:
33
AF XY:
0.000892
AC XY:
648
AN XY:
726688
show subpopulations
Gnomad4 AFR exome
AF:
0.0422
Gnomad4 AMR exome
AF:
0.000896
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000812
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000900
Gnomad4 OTH exome
AF:
0.00164
GnomAD4 genome
AF:
0.0104
AC:
1588
AN:
151986
Hom.:
36
Cov.:
32
AF XY:
0.00984
AC XY:
731
AN XY:
74280
show subpopulations
Gnomad4 AFR
AF:
0.0371
Gnomad4 AMR
AF:
0.00217
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000442
Gnomad4 OTH
AF:
0.00568
Alfa
AF:
0.00215
Hom.:
6
Bravo
AF:
0.0122
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ESP6500AA
AF:
0.0409
AC:
180
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.00358
AC:
435
Asia WGS
AF:
0.00202
AC:
7
AN:
3478

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:2
Benign, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Jan 08, 2015- -
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Oculocutaneous albinism type 3 Benign:2
Benign, criteria provided, single submitterclinical testingMendelicsMay 28, 2019- -
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaApr 27, 2017This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -
not provided Benign:2
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 31, 2024- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Oculocutaneous albinism type 3;C2677086:MELANESIAN BLOND HAIR Benign:1
Likely benign, criteria provided, single submitterclinical testingFulgent Genetics, Fulgent GeneticsNov 01, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
0.16
D
BayesDel_noAF
Pathogenic
0.48
CADD
Pathogenic
36
DANN
Uncertain
0.99
Eigen
Uncertain
0.34
Eigen_PC
Benign
0.089
FATHMM_MKL
Uncertain
0.86
D
MutationTaster
Benign
1.0
D;D;D
Vest4
0.87
GERP RS
2.6

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs41302073; hg19: chr9-12709125; API