NM_003797.5:c.635-2275T>C

Variant names:

• chr11-86261897-T-C
• rs10898459
• NM_003797.5:c.635-2275T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 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=-0.92).
• 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 rank	MANE	Protein	UniProt
EED	NM_003797.5	c.635-2275T>C		intron_variant	Intron 6 of 11	ENST00000263360.11	NP_003788.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EED	ENST00000263360.11	c.635-2275T>C		intron_variant	Intron 6 of 11	1	NM_003797.5	ENSP00000263360.6

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

African (AFR) AF: 0.386 AC: 16007 AN: 41454

American (AMR) AF: 0.402 AC: 6132 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1053 AN: 3468

East Asian (EAS) AF: 0.506 AC: 2619 AN: 5172

South Asian (SAS) AF: 0.455 AC: 2190 AN: 4808

European-Finnish (FIN) AF: 0.423 AC: 4471 AN: 10558

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.414 AC: 28130 AN: 67948

Other (OTH) AF: 0.411 AC: 867 AN: 2112

Alfa AF: 0.407 Hom.: 40166

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
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs10898459; hg19: chr11-85972939;