11-86245217-G-C

Variant names:

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

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>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,609,616 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: 𝑓 0.0000066 (0 hom., cov: 30)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: EED NM_003797.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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=-0.32).

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>C		5_prime_UTR	Exon 1 of 12	NP_003788.2
	EED	NM_001308007.2		c.-13G>C		5_prime_UTR	Exon 1 of 13	NP_001294936.1	O75530-2
	EED	NM_001440587.1		c.-13G>C		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>C		5_prime_UTR	Exon 1 of 12	ENSP00000263360.6	O75530-1
	EED	ENST00000327320.8	TSL:1	c.-13G>C		5_prime_UTR	Exon 1 of 11	ENSP00000315587.4	O75530-3
	EED	ENST00000673233.3		c.168G>C	p.Gly56Gly	synonymous	Exon 1 of 12	ENSP00000500914.2	A0A5F9ZI63

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152002 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000241

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457614 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 725166

African (AFR) AF: 0.0000301 AC: 1 AN: 33188

American (AMR) AF: 0.00 AC: 0 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: 0.00 AC: 0 AN: 1109810

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

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152002 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 74248

African (AFR) AF: 0.0000241 AC: 1 AN: 41412

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5126

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67978

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	20
DANN	Benign	0.95
PhyloP100		3.4
PromoterAI		-0.060	Neutral

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

Other links and lift over

dbSNP: rs760817291; hg19: chr11-85956259;