rs9971532

Positions:

• chr11-86218448-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
		n.86218448G>A		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EED	ENST00000707108.1	c.9+11970G>A		intron_variant				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

Gnomad4 AFR AF: 0.0564

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.253

Gnomad4 EAS AF: 0.124

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.373

Gnomad4 NFE AF: 0.326

Gnomad4 OTH AF: 0.243

Alfa AF: 0.299 Hom.: 9729

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9971532; hg19: chr11-85929490;