rs148810263

chr2-27364580-T-Achr2-27364580-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001034116.2(EIF2B4):c.1392A>T(p.Gln464His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q464Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: EIF2B4 NM_001034116.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0420

Genes affected

EIF2B4 (HGNC:3260): (eukaryotic translation initiation factor 2B subunit delta) Eukaryotic initiation factor 2B (EIF2B), which is necessary for protein synthesis, is a GTP exchange factor composed of five different subunits. The protein encoded by this gene is the fourth, or delta, subunit. Defects in this gene are a cause of leukoencephalopathy with vanishing white matter (VWM) and ovarioleukodystrophy. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

GTF3C2-AS2 (HGNC:55699): (GTF3C2 antisense RNA 2)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.123487055).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EIF2B4	NM_001034116.2	c.1392A>T	p.Gln464His	missense_variant	13/13	ENST00000347454.9
GTF3C2-AS2	NR_183825.1	n.1746-2844T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EIF2B4	ENST00000347454.9	c.1392A>T	p.Gln464His	missense_variant	13/13	1	NM_001034116.2	P4
GTF3C2-AS2	ENST00000412749.1	n.201-2844T>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.36
Cadd	Benign	18
Dann	Benign	0.96
DEOGEN2	Benign	0.0094	T;T;.;.;T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.58	D
LIST_S2	Uncertain	0.92	D;D;D;D;D
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.12	T;T;T;T;T
MetaSVM	Benign	-0.34	T
MutationTaster	Benign	0.94	N;N;N;N
PrimateAI	Benign	0.40	T
Sift4G	Benign	0.17	T;T;T;T;T
Polyphen		0.0, 0.072, 0.13	.;B;B;B;.
Vest4		0.065
MutPred		0.38		.;Loss of sheet (P = 0.1158);.;.;.;
MVP		0.47
MPC		0.49
ClinPred		0.21	T
GERP RS		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.63

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: rs148810263; hg19: chr2-27587447;