chr10-117547867-G-C

Variant names:

• chr10-117547867-G-C
• rs740734
• NM_004098.4:c.592-198G>C

Variant summary

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

The NM_004098.4(EMX2):​c.592-198G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,048 control chromosomes in the GnomAD database, including 3,562 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 0.21 (3562 hom., cov: 32)
• Consequence: EMX2 NM_004098.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.466

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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EMX2	NM_004098.4	c.592-198G>C		intron_variant	Intron 2 of 2	ENST00000553456.5	NP_004089.1
EMX2	NM_001165924.2	c.407-198G>C		intron_variant	Intron 1 of 1		NP_001159396.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EMX2	ENST00000553456.5	c.592-198G>C		intron_variant	Intron 2 of 2	1	NM_004098.4	ENSP00000450962.3
EMX2	ENST00000546446.2	n.551-198G>C		intron_variant	Intron 2 of 2	1
EMX2	ENST00000442245.5	c.407-198G>C		intron_variant	Intron 1 of 1	2		ENSP00000474874.1
EMX2	ENST00000616794.1	c.107-198G>C		intron_variant	Intron 1 of 1	2		ENSP00000480271.1

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31605 AN: 151932 Hom.: 3557 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.183

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.208 AC: 31630 AN: 152048 Hom.: 3562 Cov.: 32 AF XY: 0.213 AC XY: 15823 AN XY: 74330

Gnomad4 AFR AF: 0.154

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.281

Gnomad4 EAS AF: 0.188

Gnomad4 SAS AF: 0.388

Gnomad4 FIN AF: 0.233

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.183

Alfa AF: 0.199 Hom.: 403

Bravo AF: 0.198

Asia WGS AF: 0.283 AC: 984 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.5
DANN	Benign	0.52

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: rs740734; hg19: chr10-119307378;