dbSNP rs365446: EMX2:c.407-828G>C (chr10-117544804-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004098.4(EMX2):c.407-828G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 152,062 control chromosomes in the GnomAD database, including 29,092 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 0.62 ( 29081 hom., cov: 33)

Exomes 𝑓: 0.71 ( 11 hom. )

Consequence

EMX2
NM_004098.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.07

Publications

2 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.659 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	UniProt
EMX2	NM_004098.4	MANE Select	c.407-828G>C	intron	N/A	NP_004089.1	Q04743-1
EMX2	NM_001165924.2		c.406+1131G>C	intron	N/A	NP_001159396.1	Q04743-2
EMX2OS	NR_002791.2		n.265C>G	non_coding_transcript_exon	Exon 1 of 4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EMX2	ENST00000553456.5	TSL:1 MANE Select	c.407-828G>C	intron	N/A	ENSP00000450962.3	Q04743-1
EMX2OS	ENST00000551288.5	TSL:1	n.265C>G	non_coding_transcript_exon	Exon 1 of 4
EMX2	ENST00000442245.5	TSL:2	c.406+1131G>C	intron	N/A	ENSP00000474874.1	Q04743-2

Frequencies

GnomAD3 genomes

AF:

0.615

AC:

93460

AN:

151906

Hom.:

29066

Cov.:

show subpopulations

Gnomad AFR

AF:

0.558

Gnomad AMI

AF:

0.668

Gnomad AMR

AF:

0.618

Gnomad ASJ

AF:

0.589

Gnomad EAS

AF:

0.572

Gnomad SAS

AF:

0.497

Gnomad FIN

AF:

0.595

Gnomad MID

AF:

0.655

Gnomad NFE

AF:

0.664

Gnomad OTH

AF:

0.647

GnomAD4 exome

AF:

0.711

AC:

AN:

Hom.:

Cov.:

AF XY:

0.711

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)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.719

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.565

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.615

AC:

93517

AN:

152024

Hom.:

29081

Cov.:

AF XY:

0.608

AC XY:

45213

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.558

AC:

23102

AN:

41412

American (AMR)

AF:

0.617

AC:

9438

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.589

AC:

2042

AN:

3468

East Asian (EAS)

AF:

0.572

AC:

2959

AN:

5170

South Asian (SAS)

AF:

0.498

AC:

2400

AN:

4822

European-Finnish (FIN)

AF:

0.595

AC:

6288

AN:

10564

Middle Eastern (MID)

AF:

0.646

AC:

190

AN:

294

European-Non Finnish (NFE)

AF:

0.664

AC:

45118

AN:

67982

Other (OTH)

AF:

0.649

AC:

1371

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1840

3680

5520

7360

9200

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

778

1556

2334

3112

3890

<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:

0.648

Hom.:

4010

Bravo

AF:

0.621

Asia WGS

AF:

0.514

AC:

1792

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.9

(source)

DANN

Benign

0.46

PhyloP100

-1.1

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