rs1681690750

Variant names:

• chr2-27364484-A-G
• rs1681690750
• NM_001034116.2:c.1488T>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001034116.2(EIF2B4):​c.1488T>C​(p.Leu496Leu) variant causes a synonymous 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: EIF2B4 NM_001034116.2 synonymous
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.12
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP7: Synonymous conserved (PhyloP=-1.12 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001034116.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF2B4	NM_001034116.2	MANE Select	c.1488T>C	p.Leu496Leu	synonymous	Exon 13 of 13	NP_001029288.1	Q9UI10-1
	EIF2B4	NM_001318965.2		c.1551T>C	p.Leu517Leu	synonymous	Exon 12 of 12	NP_001305894.1	E7ERK9
	EIF2B4	NM_172195.4		c.1548T>C	p.Leu516Leu	synonymous	Exon 12 of 12	NP_751945.2	Q9UI10-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF2B4	ENST00000347454.9	TSL:1 MANE Select	c.1488T>C	p.Leu496Leu	synonymous	Exon 13 of 13	ENSP00000233552.6	Q9UI10-1
	EIF2B4	ENST00000451130.6	TSL:1	c.1548T>C	p.Leu516Leu	synonymous	Exon 12 of 12	ENSP00000394869.2	Q9UI10-2
	EIF2B4	ENST00000445933.6	TSL:1	c.1485T>C	p.Leu495Leu	synonymous	Exon 13 of 13	ENSP00000394397.2	Q9UI10-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Vanishing white matter disease (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.55
DANN	Benign	0.55
PhyloP100		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1681690750; hg19: chr2-27587351;