11-89284958-A-G
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBS2_Supporting
The NM_000372.5(TYR):c.1366+4A>G variant causes a splice region, intron change. The variant allele was found at a frequency of 0.00234 in 1,610,256 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000372.5 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00163 AC: 247AN: 151868Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00150 AC: 374AN: 249624Hom.: 0 AF XY: 0.00141 AC XY: 191AN XY: 134994
GnomAD4 exome AF: 0.00241 AC: 3521AN: 1458270Hom.: 9 Cov.: 30 AF XY: 0.00235 AC XY: 1706AN XY: 725590
GnomAD4 genome AF: 0.00163 AC: 247AN: 151986Hom.: 0 Cov.: 32 AF XY: 0.00159 AC XY: 118AN XY: 74304
ClinVar
Submissions by phenotype
not provided Uncertain:3Benign:1Other:1
not provided, no classification provided | literature only | Retina International | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 03, 2025 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2024 | TYR: PM2, BP4 - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jan 13, 2016 | The c.1366+4A>G variant in the TYR gene has been reported previously in the heterozygous state in an individual with oculocutaneous albinism type 1B (Hutton et al., 2008). This variant reduces the quality of the splice donor site in intron 4, and is expected to cause abnormal gene splicing. However, the NHLBI Exome Sequencing Project reports that c.1366+4A>G was observed in 23/8592 alleles (0.26%) from individuals of European American ancestry, including one homozygous individual within this control population. Based on the currently available data, we interpret c.1366+4A>G as a variant of uncertain significance. - |
Oculocutaneous albinism Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This 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). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Oculocutaneous albinism type 1A Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 22, 2021 | - - |
Oculocutaneous albinism type 1B;C2677190:SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN;C4551504:Oculocutaneous albinism type 1A;CN028925:Ocular albinism with congenital sensorineural hearing loss Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at