chr2-27367799-C-A

Variant names:

• chr2-27367799-C-A
• rs41288829
• NM_001034116.2:c.729G>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001034116.2(EIF2B4):​c.729G>T​(p.Pro243Pro) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P243P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EIF2B4 NM_001034116.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.381
• 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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.105630934).
• BP7: Synonymous conserved (PhyloP=-0.381 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.729G>T	p.Pro243Pro	synonymous	Exon 8 of 13	NP_001029288.1
	EIF2B4	NM_001318965.2		c.792G>T	p.Pro264Pro	synonymous	Exon 7 of 12	NP_001305894.1
	EIF2B4	NM_172195.4		c.789G>T	p.Pro263Pro	synonymous	Exon 7 of 12	NP_751945.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF2B4	ENST00000347454.9	TSL:1 MANE Select	c.729G>T	p.Pro243Pro	synonymous	Exon 8 of 13	ENSP00000233552.6
	EIF2B4	ENST00000451130.6	TSL:1	c.789G>T	p.Pro263Pro	synonymous	Exon 7 of 12	ENSP00000394869.2
	EIF2B4	ENST00000445933.6	TSL:1	c.726G>T	p.Pro242Pro	synonymous	Exon 8 of 13	ENSP00000394397.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	2.7
DANN	Benign	0.83
FATHMM_MKL	Benign	0.074	N
LIST_S2	Benign	0.27	T
MetaRNN	Benign	0.11	T
PhyloP100		-0.38
Vest4		0.16
MVP		0.65
GERP RS		-7.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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: rs41288829; hg19: chr2-27590666;