rs8192640

Positions:

• chr10-117545494-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_004098.4(EMX2):​c.407-138C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0163 in 1,072,236 control chromosomes in the GnomAD database, including 188 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 0.013 (26 hom., cov: 33)
  • Exomes 𝑓: 0.017 (162 hom.)
• Consequence: EMX2 NM_004098.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.81

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0133 (2024/152330) while in subpopulation NFE AF= 0.0204 (1390/68024). AF 95% confidence interval is 0.0195. There are 26 homozygotes in gnomad4. There are 948 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2024 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EMX2	NM_004098.4	c.407-138C>T		intron_variant		ENST00000553456.5	NP_004089.1
EMX2	NM_001165924.2	c.406+1821C>T		intron_variant			NP_001159396.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EMX2	ENST00000553456.5	c.407-138C>T		intron_variant		1	NM_004098.4	ENSP00000450962.3
EMX2	ENST00000546446.2	n.366-138C>T		intron_variant		1
EMX2	ENST00000442245.5	c.406+1821C>T		intron_variant		2		ENSP00000474874.1
EMX2	ENST00000616794.1	c.106+1821C>T		intron_variant		2		ENSP00000480271.1

Frequencies

GnomAD3 genomes AF: 0.0133 AC: 2026 AN: 152212 Hom.: 26 Cov.: 33

Gnomad AFR AF: 0.00285

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0142

Gnomad ASJ AF: 0.0124

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.00703

Gnomad FIN AF: 0.0185

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0204

Gnomad OTH AF: 0.00860

GnomAD4 exome AF: 0.0168 AC: 15430 AN: 919906 Hom.: 162 AF XY: 0.0166 AC XY: 7675 AN XY: 461226

Gnomad4 AFR exome AF: 0.00247

Gnomad4 AMR exome AF: 0.0101

Gnomad4 ASJ exome AF: 0.00972

Gnomad4 EAS exome AF: 0.0000604

Gnomad4 SAS exome AF: 0.0113

Gnomad4 FIN exome AF: 0.0192

Gnomad4 NFE exome AF: 0.0188

Gnomad4 OTH exome AF: 0.0152

GnomAD4 genome AF: 0.0133 AC: 2024 AN: 152330 Hom.: 26 Cov.: 33 AF XY: 0.0127 AC XY: 948 AN XY: 74486

Gnomad4 AFR AF: 0.00284

Gnomad4 AMR AF: 0.0142

Gnomad4 ASJ AF: 0.0124

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.00683

Gnomad4 FIN AF: 0.0185

Gnomad4 NFE AF: 0.0204

Gnomad4 OTH AF: 0.00851

Alfa AF: 0.0204 Hom.: 9

Bravo AF: 0.0123

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	5.9
DANN	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs8192640; hg19: chr10-119305005;