chr18-21384251-G-T
Variant names:
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 1P and 7B. PP2BP4_ModerateBP6BS2
The NM_001142966.3(GREB1L):c.203G>T(p.Arg68Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000143 in 1,551,274 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00015 ( 0 hom. )
Consequence
GREB1L
NM_001142966.3 missense
NM_001142966.3 missense
Scores
4
15
Clinical Significance
Conservation
PhyloP100: 5.34
Genes affected
GREB1L (HGNC:31042): (GREB1 like retinoic acid receptor coactivator) Acts upstream of or within kidney development. Predicted to be integral component of membrane. Implicated in autosomal dominant nonsyndromic deafness and renal agenesis. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
PP2
Missense variant in the GREB1L gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 17 curated pathogenic missense variants (we use a threshold of 10). The gene has 23 curated benign missense variants. Gene score misZ: 5.3659 (above the threshold of 3.09). Trascript score misZ: 5.6738 (above the threshold of 3.09). GenCC associations: The gene is linked to bilateral renal agenesis, renal hypodysplasia/aplasia 3, renal agenesis, unilateral, hearing loss, autosomal dominant 80.
BP4
Computational evidence support a benign effect (MetaRNN=0.15200263).
BP6
Variant 18-21384251-G-T is Benign according to our data. Variant chr18-21384251-G-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2432267.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.
BS2
High AC in GnomAd4 at 19 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GREB1L | NM_001142966.3 | c.203G>T | p.Arg68Leu | missense_variant | Exon 4 of 33 | ENST00000424526.7 | NP_001136438.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000125 AC: 19AN: 152116Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000831 AC: 13AN: 156492Hom.: 0 AF XY: 0.0000723 AC XY: 6AN XY: 82940
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GnomAD4 exome AF: 0.000145 AC: 203AN: 1399040Hom.: 0 Cov.: 31 AF XY: 0.000116 AC XY: 80AN XY: 690054
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GnomAD4 genome AF: 0.000125 AC: 19AN: 152234Hom.: 0 Cov.: 32 AF XY: 0.0000940 AC XY: 7AN XY: 74450
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Nov 29, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 27, 2024 | - - |
GREB1L-related disorder Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 25, 2023 | The GREB1L c.203G>T variant is predicted to result in the amino acid substitution p.Arg68Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.021% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/18-18964212-G-T). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
D;D;.
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;.
REVEL
Benign
Sift
Uncertain
D;T;.
Sift4G
Benign
T;T;T
Polyphen
P;.;P
Vest4
MVP
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at