11-86245217-G-T

Variant names:

• chr11-86245217-G-T
• rs760817291
• NM_003797.5:c.-13G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003797.5(EED):​c.-13G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,457,614 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: EED NM_003797.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.40
• Publications: 0 publications found

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]

EED Gene-Disease associations (from GenCC):

• Cohen-Gibson syndrome

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), ClinGen
• Weaver syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000288809 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003797.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EED	NM_003797.5	MANE Select	c.-13G>T		5_prime_UTR	Exon 1 of 12	NP_003788.2
	EED	NM_001308007.2		c.-13G>T		5_prime_UTR	Exon 1 of 13	NP_001294936.1	O75530-2
	EED	NM_001440587.1		c.-13G>T		5_prime_UTR	Exon 1 of 12	NP_001427516.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EED	ENST00000263360.11	TSL:1 MANE Select	c.-13G>T		5_prime_UTR	Exon 1 of 12	ENSP00000263360.6	O75530-1
	EED	ENST00000327320.8	TSL:1	c.-13G>T		5_prime_UTR	Exon 1 of 11	ENSP00000315587.4	O75530-3
	EED	ENST00000673233.3		c.168G>T	p.Gly56Gly	synonymous	Exon 1 of 12	ENSP00000500914.2	A0A5F9ZI63

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1457614 Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 2 AN XY: 725166

African (AFR) AF: 0.00 AC: 0 AN: 33188

American (AMR) AF: 0.0000225 AC: 1 AN: 44368

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26026

East Asian (EAS) AF: 0.00 AC: 0 AN: 39158

South Asian (SAS) AF: 0.00 AC: 0 AN: 86046

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53082

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5722

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1109810

Other (OTH) AF: 0.00 AC: 0 AN: 60214

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	20
DANN	Benign	0.97
PhyloP100		3.4
PromoterAI		-0.11	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs760817291; hg19: chr11-85956259;