chr3-184141151-A-C

Variant names:

• chr3-184141151-A-C
• rs865808
• NM_003907.3:c.1156+421A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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]

EIF2B5-DT (HGNC:55202): (EIF2B5 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003907.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF2B5	NM_003907.3	MANE Select	c.1156+421A>C		intron	N/A	NP_003898.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF2B5	ENST00000648915.2	MANE Select	c.1156+421A>C		intron	N/A	ENSP00000497160.1
	EIF2B5	ENST00000481054.5	TSL:1	n.1250+421A>C		intron	N/A
	EIF2B5	ENST00000647909.1		c.1180+421A>C		intron	N/A	ENSP00000498164.1

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

African (AFR) AF: 0.472 AC: 19590 AN: 41486

American (AMR) AF: 0.501 AC: 7664 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.481 AC: 1667 AN: 3468

East Asian (EAS) AF: 0.544 AC: 2809 AN: 5168

South Asian (SAS) AF: 0.570 AC: 2749 AN: 4820

European-Finnish (FIN) AF: 0.360 AC: 3805 AN: 10566

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.531 AC: 36098 AN: 67992

Other (OTH) AF: 0.492 AC: 1037 AN: 2108

Alfa AF: 0.525 Hom.: 41083

Bravo AF: 0.506

Asia WGS AF: 0.574 AC: 1996 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.22
DANN	Benign	0.71
PhyloP100		-1.3
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: rs865808; hg19: chr3-183858939;