rs365446

Variant names:

• chr10-117544804-G-C
• rs365446
• ENST00000551288.5:n.265C>G

Your query was ambiguous. Multiple possible variants found:

• chr10-117544804-G-C
• chr10-117544804-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000551288.5(EMX2OS):​n.265C>G variant causes a non coding transcript exon 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: EMX2OS ENST00000551288.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 2 publications found

Genes affected

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

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 Gene-Disease associations (from GenCC):

• schizencephaly

  Inheritance: AD, Unknown Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EMX2	NM_004098.4	c.407-828G>C		intron_variant	Intron 1 of 2	ENST00000553456.5	NP_004089.1
EMX2OS	NR_002791.2	n.265C>G		non_coding_transcript_exon_variant	Exon 1 of 4
EMX2	NM_001165924.2	c.406+1131G>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.407-828G>C		intron_variant	Intron 1 of 2	1	NM_004098.4	ENSP00000450962.3

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93460 AN: 151906 Hom.: 29066 Cov.: 33

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: 27 AN: 38 Hom.: 11 Cov.: 0 AF XY: 0.711 AC XY: 27 AN XY: 38

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.719 AC: 23 AN: 32

Other (OTH) AF: 1.00 AC: 4 AN: 4

GnomAD4 genome AF: 0.615 AC: 93517 AN: 152024 Hom.: 29081 Cov.: 33 AF XY: 0.608 AC XY: 45213 AN XY: 74326

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

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.9
DANN	Benign	0.46
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs365446; hg19: chr10-119304315;