Genetic Variant NM_003797.5:c.-13G>A (chr11-86245217-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_003797.5(EED):c.-13G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000491 in 1,609,616 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000051 ( 1 hom. )

Consequence

EED
NM_003797.5 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.40

Publications

0 publications found

Variant links:

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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), ClinGen
Weaver syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

EED links:

ENSG00000288809 (HGNC:):

ENSG00000288809 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.28).

BP6

Variant 11-86245217-G-A is Benign according to our data. Variant chr11-86245217-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2642249.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 5 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003797.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EED	NM_003797.5	MANE Select	c.-13G>A	5_prime_UTR	Exon 1 of 12	NP_003788.2
EED	NM_001308007.2		c.-13G>A	5_prime_UTR	Exon 1 of 13	NP_001294936.1	O75530-2
EED	NM_001440587.1		c.-13G>A	5_prime_UTR	Exon 1 of 12	NP_001427516.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EED	ENST00000263360.11	TSL:1 MANE Select	c.-13G>A		5_prime_UTR	Exon 1 of 12	ENSP00000263360.6	O75530-1
EED	ENST00000327320.8	TSL:1	c.-13G>A		5_prime_UTR	Exon 1 of 11	ENSP00000315587.4	O75530-3
EED	ENST00000673233.3		c.168G>A	p.Gly56Gly	synonymous	Exon 1 of 12	ENSP00000500914.2	A0A5F9ZI63

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152002

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000410

AC:

AN:

244006

AF XY:

0.0000527

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000915

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000508

AC:

AN:

1457614

Hom.:

Cov.:

AF XY:

0.0000579

AC XY:

AN XY:

725166

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33188

American (AMR)

AF:

0.00

AC:

AN:

44368

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26026

East Asian (EAS)

AF:

0.00

AC:

AN:

39158

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86046

European-Finnish (FIN)

AF:

0.0000188

AC:

AN:

53082

Middle Eastern (MID)

AF:

0.000175

AC:

AN:

5722

European-Non Finnish (NFE)

AF:

0.0000532

AC:

AN:

1109810

Other (OTH)

AF:

0.000199

AC:

AN:

60214

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152002

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74248

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41412

American (AMR)

AF:

0.00

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5126

South Asian (SAS)

AF:

0.000207

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

67978

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000302

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Uncertain

0.98

PhyloP100

3.4

PromoterAI

0.031

Neutral

(source)

Mutation Taster

=285/15

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over