rs9971532

Variant names:

• chr11-86218448-G-A
• rs9971532
• ENST00000707108.1:c.9+11970G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000707108.1(EED):​c.9+11970G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 152,144 control chromosomes in the GnomAD database, including 5,221 homozygotes. 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 0.23 (5221 hom., cov: 32)
• Consequence: EED ENST00000707108.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• Publications: 14 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, ClinGen
• Weaver syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EED	ENST00000707108.1	c.9+11970G>A		intron_variant	Intron 2 of 12			ENSP00000516737.1

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35231 AN: 152026 Hom.: 5222 Cov.: 32

Gnomad AFR AF: 0.0566

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.245

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.232 AC: 35230 AN: 152144 Hom.: 5221 Cov.: 32 AF XY: 0.233 AC XY: 17322 AN XY: 74350

African (AFR) AF: 0.0564 AC: 2343 AN: 41550

American (AMR) AF: 0.217 AC: 3319 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 876 AN: 3468

East Asian (EAS) AF: 0.124 AC: 645 AN: 5188

South Asian (SAS) AF: 0.223 AC: 1077 AN: 4820

European-Finnish (FIN) AF: 0.373 AC: 3927 AN: 10540

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.326 AC: 22178 AN: 67976

Other (OTH) AF: 0.243 AC: 512 AN: 2110

Alfa AF: 0.278 Hom.: 13816

Bravo AF: 0.211

Asia WGS AF: 0.166 AC: 576 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	9.3
DANN	Benign	0.78
PhyloP100		0.30

Splicing

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

Other links and lift over

dbSNP: rs9971532; hg19: chr11-85929490;