11-86250124-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003797.5(EED):c.115-172C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 151,966 control chromosomes in the GnomAD database, including 9,881 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.35 (9881 hom., cov: 33)
• Consequence: EED NM_003797.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.884

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 11-86250124-C-T is Benign according to our data. Variant chr11-86250124-C-T is described in ClinVar as [Benign]. Clinvar id is 1226792.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EED	NM_003797.5	c.115-172C>T		intron_variant		ENST00000263360.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EED	ENST00000263360.11	c.115-172C>T		intron_variant		1	NM_003797.5	P1

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53445 AN: 151848 Hom.: 9878 Cov.: 33

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.362

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

GnomAD4 genome AF: 0.352 AC: 53482 AN: 151966 Hom.: 9881 Cov.: 33 AF XY: 0.352 AC XY: 26179 AN XY: 74278

Gnomad4 AFR AF: 0.246

Gnomad4 AMR AF: 0.310

Gnomad4 ASJ AF: 0.296

Gnomad4 EAS AF: 0.344

Gnomad4 SAS AF: 0.405

Gnomad4 FIN AF: 0.425

Gnomad4 NFE AF: 0.412

Gnomad4 OTH AF: 0.358

Alfa AF: 0.390 Hom.: 1533

Bravo AF: 0.339

Asia WGS AF: 0.339 AC: 1177 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 11, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.46
Dann	Benign	0.23

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: rs2270680; hg19: chr11-85961166;