rs855769

chr10-117544585-A-Gchr10-117544585-A-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.76

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]

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

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EMX2	NM_004098.4	c.406+912A>G		intron_variant		ENST00000553456.5
EMX2OS	NR_002791.2	n.484T>C		non_coding_transcript_exon_variant	1/4
EMX2	NM_001165924.2	c.406+912A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EMX2	ENST00000553456.5	c.406+912A>G		intron_variant		1	NM_004098.4	P1
EMX2OS	ENST00000551288.5	n.484T>C		non_coding_transcript_exon_variant	1/4	1
EMX2	ENST00000442245.5	c.406+912A>G		intron_variant		2
EMX2	ENST00000616794.1	c.106+912A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45860 AN: 151874 Hom.: 7214 Cov.: 32

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: 4 AN: 6 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 2 AN XY: 4

Gnomad4 NFE exome AF: 0.667

GnomAD4 genome AF: 0.302 AC: 45879 AN: 151992 Hom.: 7217 Cov.: 32 AF XY: 0.309 AC XY: 22966 AN XY: 74288

Gnomad4 AFR AF: 0.335

Gnomad4 AMR AF: 0.314

Gnomad4 ASJ AF: 0.298

Gnomad4 EAS AF: 0.377

Gnomad4 SAS AF: 0.428

Gnomad4 FIN AF: 0.340

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.269

Alfa AF: 0.270 Hom.: 1154

Bravo AF: 0.295

Asia WGS AF: 0.395 AC: 1370 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
Cadd	Benign	14
Dann	Benign	0.67

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: rs855769; hg19: chr10-119304096;