rs10898459

chr11-86261897-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003797.5(EED):c.635-2275T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 151,988 control chromosomes in the GnomAD database, including 12,795 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 0.41 (12795 hom., cov: 31)
• Consequence: EED NM_003797.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EED	NM_003797.5	c.635-2275T>C		intron_variant		ENST00000263360.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EED	ENST00000263360.11	c.635-2275T>C		intron_variant		1	NM_003797.5	P1

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61992 AN: 151870 Hom.: 12790 Cov.: 31

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.506

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.414

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

GnomAD4 genome AF: 0.408 AC: 62035 AN: 151988 Hom.: 12795 Cov.: 31 AF XY: 0.410 AC XY: 30430 AN XY: 74280

Gnomad4 AFR AF: 0.386

Gnomad4 AMR AF: 0.402

Gnomad4 ASJ AF: 0.304

Gnomad4 EAS AF: 0.506

Gnomad4 SAS AF: 0.455

Gnomad4 FIN AF: 0.423

Gnomad4 NFE AF: 0.414

Gnomad4 OTH AF: 0.411

Alfa AF: 0.407 Hom.: 26372

Bravo AF: 0.407

Asia WGS AF: 0.441 AC: 1534 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.1
Dann	Benign	0.72

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: rs10898459; hg19: chr11-85972939;