chr11-86245240-G-T
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4
The NM_003797.5(EED):c.11G>T(p.Arg4Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000093 in 1,613,290 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R4K) has been classified as Uncertain significance.
Frequency
Consequence
NM_003797.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EED | NM_003797.5 | c.11G>T | p.Arg4Met | missense_variant | 1/12 | ENST00000263360.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EED | ENST00000263360.11 | c.11G>T | p.Arg4Met | missense_variant | 1/12 | 1 | NM_003797.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152036Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.0000162 AC: 4AN: 247112Hom.: 0 AF XY: 0.0000224 AC XY: 3AN XY: 134160
GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461254Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7AN XY: 726912
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152036Hom.: 0 Cov.: 30 AF XY: 0.0000269 AC XY: 2AN XY: 74256
ClinVar
Submissions by phenotype
Cohen-Gibson syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 07, 2022 | This variant has not been reported in the literature in individuals affected with EED-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant is present in population databases (rs766472086, gnomAD 0.004%). This sequence change replaces arginine, which is basic and polar, with methionine, which is neutral and non-polar, at codon 4 of the EED protein (p.Arg4Met). - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 16, 2023 | The c.11G>T (p.R4M) alteration is located in exon 1 (coding exon 1) of the EED gene. This alteration results from a G to T substitution at nucleotide position 11, causing the arginine (R) at amino acid position 4 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at