rs182106684

chr11-86250379-A-G

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_003797.5(EED):c.198A>G(p.Lys66=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000454 in 1,608,864 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 Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000041 (0 hom.)
• Consequence: EED NM_003797.5 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.50

Genes affected

EED (HGNC:3188): (embryonic ectoderm development) This gene encodes a member of the Polycomb-group (PcG) family. PcG family members form multimeric protein complexes, which are involved in maintaining the transcriptional repressive state of genes over successive cell generations. This protein interacts with enhancer of zeste 2, the cytoplasmic tail of integrin beta7, immunodeficiency virus type 1 (HIV-1) MA protein, and histone deacetylase proteins. This protein mediates repression of gene activity through histone deacetylation, and may act as a specific regulator of integrin function. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 11-86250379-A-G is Benign according to our data. Variant chr11-86250379-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 544590.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=3.49 with no splicing effect.
• BS2: High AC in GnomAd at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EED	NM_003797.5	c.198A>G	p.Lys66=	synonymous_variant	2/12	ENST00000263360.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EED	ENST00000263360.11	c.198A>G	p.Lys66=	synonymous_variant	2/12	1	NM_003797.5	P1

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152236 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.000132

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000857 AC: 21 AN: 245080 Hom.: 0 AF XY: 0.0000753 AC XY: 10 AN XY: 132778

Gnomad AFR exome AF: 0.000255

Gnomad AMR exome AF: 0.0000304

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000335

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000134

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000412 AC: 60 AN: 1456510 Hom.: 0 Cov.: 30 AF XY: 0.0000400 AC XY: 29 AN XY: 724608

Gnomad4 AFR exome AF: 0.0000909

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000460

Gnomad4 OTH exome AF: 0.0000664

GnomAD4 genome AF: 0.0000853 AC: 13 AN: 152354 Hom.: 0 Cov.: 33 AF XY: 0.000107 AC XY: 8 AN XY: 74508

Gnomad4 AFR AF: 0.0000962

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000153 Hom.: 0

Bravo AF: 0.0000793

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Cohen-Gibson syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 22, 2017

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2023

EED: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
Cadd	Benign	8.0
Dann	Benign	0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs182106684; hg19: chr11-85961421;