chr10-117547956-G-A

Position:

• chr10-117547956-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000553456.5(EMX2):​c.592-109G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0866 in 1,473,990 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 0.12 (1392 hom., cov: 31)
  • Exomes 𝑓: 0.083 (5826 hom.)
• Consequence: EMX2 ENST00000553456.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.238

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EMX2	NM_004098.4	c.592-109G>A		intron_variant		ENST00000553456.5	NP_004089.1
EMX2	NM_001165924.2	c.407-109G>A		intron_variant			NP_001159396.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EMX2	ENST00000553456.5	c.592-109G>A		intron_variant		1	NM_004098.4	ENSP00000450962	P1
EMX2	ENST00000546446.2	n.551-109G>A		intron_variant, non_coding_transcript_variant		1
EMX2	ENST00000442245.5	c.407-109G>A		intron_variant		2		ENSP00000474874
EMX2	ENST00000616794.1	c.107-109G>A		intron_variant		2		ENSP00000480271

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18275 AN: 151846 Hom.: 1390 Cov.: 31

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.0209

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.0619

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.0806

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0734

Gnomad OTH AF: 0.116

GnomAD4 exome AF: 0.0827 AC: 109337 AN: 1322026 Hom.: 5826 AF XY: 0.0818 AC XY: 53665 AN XY: 655938

Gnomad4 AFR exome AF: 0.202

Gnomad4 AMR exome AF: 0.130

Gnomad4 ASJ exome AF: 0.0646

Gnomad4 EAS exome AF: 0.261

Gnomad4 SAS exome AF: 0.0815

Gnomad4 FIN exome AF: 0.136

Gnomad4 NFE exome AF: 0.0694

Gnomad4 OTH exome AF: 0.0941

GnomAD4 genome AF: 0.120 AC: 18285 AN: 151964 Hom.: 1392 Cov.: 31 AF XY: 0.122 AC XY: 9097 AN XY: 74278

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.0619

Gnomad4 EAS AF: 0.224

Gnomad4 SAS AF: 0.0806

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.0734

Gnomad4 OTH AF: 0.116

Alfa AF: 0.104 Hom.: 129

Bravo AF: 0.124

Asia WGS AF: 0.161 AC: 556 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	13
DANN	Benign	0.72

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

LitVar

Other links and lift over

dbSNP: rs855768; hg19: chr10-119307467;