Genetic Variant EMX2:c.406+912A>G (chr10-117544585-A-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_004098.4(EMX2):c.406+912A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 151,998 control chromosomes in the GnomAD database, including 7,218 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 0.30 ( 7217 hom., cov: 32)

Exomes 𝑓: 0.67 ( 1 hom. )

Consequence

EMX2
NM_004098.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.76

Publications

5 publications found

Variant links:

Genes affected

EMX2 (HGNC:3341): (empty spiracles homeobox 2) This gene encodes a homeobox-containing transcription factor that is the homolog to the 'empty spiracles' gene in Drosophila. Research on this gene in humans has focused on its expression in three tissues: dorsal telencephalon, olfactory neuroepithelium, and urogenetial system. It is expressed in the dorsal telencephalon during development in a low rostral-lateral to high caudal-medial gradient and is proposed to pattern the neocortex into defined functional areas. It is also expressed in embryonic and adult olfactory neuroepithelia where it complexes with eukaryotic translation initiation factor 4E (eIF4E) and possibly regulates mRNA transport or translation. In the developing urogenital system, it is expressed in epithelial tissues and is negatively regulated by HOXA10. Alternative splicing results in multiple transcript variants encoding distinct proteins.[provided by RefSeq, Sep 2009]

EMX2 links:

EMX2OS (HGNC:18511): (EMX2 opposite strand/antisense RNA)

EMX2OS links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004098.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
EMX2	NM_004098.4	MANE Select	c.406+912A>G	intron	N/A	NP_004089.1
EMX2	NM_001165924.2		c.406+912A>G	intron	N/A	NP_001159396.1
EMX2OS	NR_002791.2		n.484T>C	non_coding_transcript_exon	Exon 1 of 4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
EMX2	ENST00000553456.5	TSL:1 MANE Select	c.406+912A>G	intron	N/A	ENSP00000450962.3
EMX2OS	ENST00000551288.5	TSL:1	n.484T>C	non_coding_transcript_exon	Exon 1 of 4
EMX2	ENST00000442245.5	TSL:2	c.406+912A>G	intron	N/A	ENSP00000474874.1

Frequencies

GnomAD3 genomes

AF:

0.302

AC:

45860

AN:

151874

Hom.:

7214

Cov.:

show subpopulations

Gnomad AFR

AF:

0.336

Gnomad AMI

AF:

0.264

Gnomad AMR

AF:

0.313

Gnomad ASJ

AF:

0.298

Gnomad EAS

AF:

0.377

Gnomad SAS

AF:

0.427

Gnomad FIN

AF:

0.340

Gnomad MID

AF:

0.209

Gnomad NFE

AF:

0.261

Gnomad OTH

AF:

0.272

GnomAD4 exome

AF:

0.667

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.667

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.600

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.302

AC:

45879

AN:

151992

Hom.:

7217

Cov.:

AF XY:

0.309

AC XY:

22966

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.335

AC:

13880

AN:

41436

American (AMR)

AF:

0.314

AC:

4800

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.298

AC:

1032

AN:

3466

East Asian (EAS)

AF:

0.377

AC:

1948

AN:

5162

South Asian (SAS)

AF:

0.428

AC:

2058

AN:

4814

European-Finnish (FIN)

AF:

0.340

AC:

3586

AN:

10540

Middle Eastern (MID)

AF:

0.214

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.260

AC:

17704

AN:

67972

Other (OTH)

AF:

0.269

AC:

567

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1625

3251

4876

6502

8127

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

464

928

1392

1856

2320

<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:

0.273

Hom.:

1205

Bravo

AF:

0.295

Asia WGS

AF:

0.395

AC:

1370

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.67

PhyloP100

1.8

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over