rs865808

Positions:

• chr3-184141151-A-C
• chr3-184141151-A-G

Variant summary

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

The NM_003907.3(EIF2B5):​c.1156+421A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 152,104 control chromosomes in the GnomAD database, including 19,275 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 0.50 (19275 hom., cov: 33)
• Consequence: EIF2B5 NM_003907.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32

Genes affected

EIF2B5 (HGNC:3261): (eukaryotic translation initiation factor 2B subunit epsilon) This gene encodes one of five subunits of eukaryotic translation initiation factor 2B (EIF2B), a GTP exchange factor for eukaryotic initiation factor 2 and an essential regulator for protein synthesis. Mutations in this gene and the genes encoding other EIF2B subunits have been associated with leukoencephalopathy with vanishing white matter. [provided by RefSeq, Nov 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF2B5	NM_003907.3	c.1156+421A>C		intron_variant		ENST00000648915.2	NP_003898.2
EIF2B5	XM_011513265.1	c.406+421A>C		intron_variant			XP_011511567.1
EIF2B5	XM_011513266.4	c.319+421A>C		intron_variant			XP_011511568.1
EIF2B5	XM_047449148.1	c.1156+421A>C		intron_variant			XP_047305104.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF2B5	ENST00000648915.2	c.1156+421A>C		intron_variant			NM_003907.3	ENSP00000497160	P2

Frequencies

GnomAD3 genomes AF: 0.500 AC: 76002 AN: 151986 Hom.: 19242 Cov.: 33

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.481

Gnomad EAS AF: 0.543

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.360

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.486

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

GnomAD4 genome AF: 0.500 AC: 76087 AN: 152104 Hom.: 19275 Cov.: 33 AF XY: 0.495 AC XY: 36847 AN XY: 74364

Gnomad4 AFR AF: 0.472

Gnomad4 AMR AF: 0.501

Gnomad4 ASJ AF: 0.481

Gnomad4 EAS AF: 0.544

Gnomad4 SAS AF: 0.570

Gnomad4 FIN AF: 0.360

Gnomad4 NFE AF: 0.531

Gnomad4 OTH AF: 0.492

Alfa AF: 0.526 Hom.: 12119

Bravo AF: 0.506

Asia WGS AF: 0.574 AC: 1996 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.22
DANN	Benign	0.71

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: rs865808; hg19: chr3-183858939;