rs182550783

Variant names:

• chr3-184135269-C-T
• rs182550783
• ENST00000491144.5:n.232C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-184135269-C-T
• chr3-184135269-C-A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000491144.5(EIF2B5):​n.232C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00227 in 1,431,932 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0017 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0023 (2 hom.)
• Consequence: EIF2B5 ENST00000491144.5 non_coding_transcript_exon
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.459
• Publications: 0 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=-0.7).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00167 (254/152372) while in subpopulation NFE AF = 0.00306 (208/68038). AF 95% confidence interval is 0.00272. There are 0 homozygotes in GnomAd4. There are 110 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000491144.5. 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
	EIF2B5	NM_003907.3	MANE Select	c.-117C>T		upstream_gene	N/A	NP_003898.2	Q13144
	EIF2B5-DT	NR_183718.1		n.-8G>A		upstream_gene	N/A
	EIF2B5-DT	NR_183719.1		n.-8G>A		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF2B5	ENST00000491144.5	TSL:2	n.232C>T		non_coding_transcript_exon	Exon 1 of 15
	EIF2B5-DT	ENST00000608135.2	TSL:5	n.149G>A		non_coding_transcript_exon	Exon 1 of 3
	EIF2B5-DT	ENST00000608232.6	TSL:5	n.21G>A		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.00167 AC: 254 AN: 152254 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00306

Gnomad OTH AF: 0.00143

GnomAD4 exome AF: 0.00234 AC: 2991 AN: 1279560 Hom.: 2 Cov.: 20 AF XY: 0.00234 AC XY: 1490 AN XY: 635736

African (AFR) AF: 0.000240 AC: 7 AN: 29150

American (AMR) AF: 0.000543 AC: 19 AN: 35018

Ashkenazi Jewish (ASJ) AF: 0.000166 AC: 4 AN: 24040

East Asian (EAS) AF: 0.00 AC: 0 AN: 35142

South Asian (SAS) AF: 0.000185 AC: 14 AN: 75660

European-Finnish (FIN) AF: 0.00142 AC: 67 AN: 47342

Middle Eastern (MID) AF: 0.000369 AC: 2 AN: 5426

European-Non Finnish (NFE) AF: 0.00287 AC: 2795 AN: 973776

Other (OTH) AF: 0.00154 AC: 83 AN: 54006

GnomAD4 genome AF: 0.00167 AC: 254 AN: 152372 Hom.: 0 Cov.: 33 AF XY: 0.00148 AC XY: 110 AN XY: 74516

African (AFR) AF: 0.000385 AC: 16 AN: 41590

American (AMR) AF: 0.000915 AC: 14 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00113 AC: 12 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00306 AC: 208 AN: 68038

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.00196 Hom.: 0

Bravo AF: 0.00143

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

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	-0.70
CADD	Benign	5.2
DANN	Benign	0.90
PhyloP100		-0.46
PromoterAI		0.036	Neutral
Mutation Taster		=300/0	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: rs182550783; hg19: chr3-183853057;