Genetic Variant EMX1:p.Ala70Glu (chr2-72918061-C-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_004097.3(EMX1):c.209C>A(p.Ala70Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000212 in 1,415,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

EMX1
NM_004097.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.39

Publications

0 publications found

Variant links:

Genes affected

EMX1 (HGNC:3340): (empty spiracles homeobox 1) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in brain development; neuron differentiation; and regulation of transcription by RNA polymerase II. Predicted to act upstream of or within several processes, including nervous system development; neuroepithelial cell differentiation; and regulation of oligodendrocyte progenitor proliferation. Located in chromosome and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

EMX1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.34221187).

BS2

High AC in GnomAdExome4 at 27 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004097.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMX1	NM_004097.3	MANE Select	c.209C>A	p.Ala70Glu	missense	Exon 1 of 3	NP_004088.2	Q04741-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EMX1	ENST00000258106.11	TSL:1 MANE Select	c.209C>A	p.Ala70Glu	missense	Exon 1 of 3	ENSP00000258106.6	Q04741-1
EMX1	ENST00000967897.1		c.209C>A	p.Ala70Glu	missense	Exon 1 of 3	ENSP00000637956.1
EMX1	ENST00000394111.6	TSL:3	c.377+1001C>A		intron	N/A	ENSP00000482619.1	A0A087WZF2

Frequencies

GnomAD3 genomes

AF:

0.0000199

AC:

AN:

150914

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000244

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000296

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000135

AC:

AN:

29632

AF XY:

0.000227

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000358

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000175

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000214

AC:

AN:

1264174

Hom.:

Cov.:

AF XY:

0.0000242

AC XY:

AN XY:

619266

show subpopulations

African (AFR)

AF:

0.0000397

AC:

AN:

25190

American (AMR)

AF:

0.000184

AC:

AN:

16268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19774

East Asian (EAS)

AF:

0.00

AC:

AN:

27772

South Asian (SAS)

AF:

0.00

AC:

AN:

61504

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30790

Middle Eastern (MID)

AF:

0.00160

AC:

AN:

3740

European-Non Finnish (NFE)

AF:

0.0000166

AC:

AN:

1026738

Other (OTH)

AF:

0.00

AC:

AN:

52398

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

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:

0.0000199

AC:

AN:

150914

Hom.:

Cov.:

AF XY:

0.0000271

AC XY:

AN XY:

73748

show subpopulations

African (AFR)

AF:

0.0000244

AC:

AN:

41056

American (AMR)

AF:

0.00

AC:

AN:

15212

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5030

South Asian (SAS)

AF:

0.00

AC:

AN:

4764

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10496

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000296

AC:

AN:

67628

Other (OTH)

AF:

0.00

AC:

AN:

2070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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:

0.0000151

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Uncertain

0.028

BayesDel_noAF

Benign

-0.20

CADD

Benign

(source)

DANN

Uncertain

0.99

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.17

FATHMM_MKL

Uncertain

0.81

M_CAP

Pathogenic

0.99

MetaRNN

Benign

0.34

MetaSVM

Uncertain

-0.28

PhyloP100

3.4

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

0.12

REVEL

Benign

0.24

Sift

Benign

0.030

Sift4G

Benign

0.68

Vest4

0.19

MVP

0.72

MPC

1.3

ClinPred

0.086

GERP RS

2.7

PromoterAI

-0.016

Neutral

(source)

gMVP

0.30

Mutation Taster

=84/16

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