rs3793975

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000263321.6(TYR):​c.1184+50G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,596,530 control chromosomes in the GnomAD database, including 14,655 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2607 hom., cov: 32)
Exomes 𝑓: 0.12 ( 12048 hom. )

Consequence

TYR
ENST00000263321.6 intron

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -0.107
Variant links:
Genes affected
TYR (HGNC:12442): (tyrosinase) The enzyme encoded by this gene catalyzes the first 2 steps, and at least 1 subsequent step, in the conversion of tyrosine to melanin. The enzyme has both tyrosine hydroxylase and dopa oxidase catalytic activities, and requires copper for function. Mutations in this gene result in oculocutaneous albinism, and nonpathologic polymorphisms result in skin pigmentation variation. The human genome contains a pseudogene similar to the 3' half of this gene. [provided by RefSeq, Oct 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BP6
Variant 11-89228020-G-A is Benign according to our data. Variant chr11-89228020-G-A is described in ClinVar as [Benign]. Clinvar id is 1281825.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TYRNM_000372.5 linkuse as main transcriptc.1184+50G>A intron_variant ENST00000263321.6 NP_000363.1
TYRXM_011542970.3 linkuse as main transcriptc.1184+50G>A intron_variant XP_011541272.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TYRENST00000263321.6 linkuse as main transcriptc.1184+50G>A intron_variant 1 NM_000372.5 ENSP00000263321 P1P14679-1

Frequencies

GnomAD3 genomes
AF:
0.167
AC:
25355
AN:
151862
Hom.:
2587
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.288
Gnomad AMI
AF:
0.0746
Gnomad AMR
AF:
0.143
Gnomad ASJ
AF:
0.118
Gnomad EAS
AF:
0.123
Gnomad SAS
AF:
0.202
Gnomad FIN
AF:
0.139
Gnomad MID
AF:
0.152
Gnomad NFE
AF:
0.108
Gnomad OTH
AF:
0.177
GnomAD3 exomes
AF:
0.140
AC:
34747
AN:
248150
Hom.:
2897
AF XY:
0.140
AC XY:
18844
AN XY:
134410
show subpopulations
Gnomad AFR exome
AF:
0.292
Gnomad AMR exome
AF:
0.132
Gnomad ASJ exome
AF:
0.118
Gnomad EAS exome
AF:
0.111
Gnomad SAS exome
AF:
0.211
Gnomad FIN exome
AF:
0.136
Gnomad NFE exome
AF:
0.109
Gnomad OTH exome
AF:
0.128
GnomAD4 exome
AF:
0.122
AC:
176056
AN:
1444552
Hom.:
12048
Cov.:
27
AF XY:
0.124
AC XY:
89574
AN XY:
719698
show subpopulations
Gnomad4 AFR exome
AF:
0.297
Gnomad4 AMR exome
AF:
0.135
Gnomad4 ASJ exome
AF:
0.118
Gnomad4 EAS exome
AF:
0.149
Gnomad4 SAS exome
AF:
0.210
Gnomad4 FIN exome
AF:
0.135
Gnomad4 NFE exome
AF:
0.107
Gnomad4 OTH exome
AF:
0.133
GnomAD4 genome
AF:
0.167
AC:
25421
AN:
151978
Hom.:
2607
Cov.:
32
AF XY:
0.168
AC XY:
12483
AN XY:
74234
show subpopulations
Gnomad4 AFR
AF:
0.288
Gnomad4 AMR
AF:
0.142
Gnomad4 ASJ
AF:
0.118
Gnomad4 EAS
AF:
0.123
Gnomad4 SAS
AF:
0.202
Gnomad4 FIN
AF:
0.139
Gnomad4 NFE
AF:
0.108
Gnomad4 OTH
AF:
0.182
Alfa
AF:
0.134
Hom.:
1004
Bravo
AF:
0.172
Asia WGS
AF:
0.191
AC:
663
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxMay 15, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
0.23
DANN
Benign
0.52

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs3793975; hg19: chr11-88961188; COSMIC: COSV54477229; API