rs2292611

Variant names:

• chr3-184135073-A-G
• rs2292611
• ENST00000491144.5:n.36A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000491144.5(EIF2B5):​n.36A>G 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 0.26 in 433,852 control chromosomes in the GnomAD database, including 16,017 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (6793 hom., cov: 32)
  • Exomes 𝑓: 0.25 (9224 hom.)
• Consequence: EIF2B5 ENST00000491144.5 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.787
• Publications: 8 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 3-184135073-A-G is Benign according to our data. Variant chr3-184135073-A-G is described in ClinVar as Benign. ClinVar VariationId is 344322.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF2B5-DT	NR_183721.1	n.189T>C		non_coding_transcript_exon_variant	Exon 1 of 2
EIF2B5-DT	NR_183718.1	n.67+122T>C		intron_variant	Intron 1 of 2
EIF2B5-DT	NR_183719.1	n.67+122T>C		intron_variant	Intron 1 of 3
EIF2B5-DT	NR_183720.1	n.104+85T>C		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF2B5	ENST00000491144.5	n.36A>G		non_coding_transcript_exon_variant	Exon 1 of 15	2
EIF2B5-DT	ENST00000609288.2	n.307T>C		non_coding_transcript_exon_variant	Exon 1 of 2	6
EIF2B5-DT	ENST00000716394.1	n.307T>C		non_coding_transcript_exon_variant	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43844 AN: 151834 Hom.: 6788 Cov.: 32

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.286

GnomAD4 exome AF: 0.245 AC: 69067 AN: 281900 Hom.: 9224 Cov.: 0 AF XY: 0.245 AC XY: 36009 AN XY: 147184

African (AFR) AF: 0.390 AC: 3426 AN: 8782

American (AMR) AF: 0.301 AC: 3299 AN: 10944

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 1796 AN: 8878

East Asian (EAS) AF: 0.409 AC: 6964 AN: 17020

South Asian (SAS) AF: 0.260 AC: 8772 AN: 33708

European-Finnish (FIN) AF: 0.323 AC: 5213 AN: 16162

Middle Eastern (MID) AF: 0.253 AC: 307 AN: 1214

European-Non Finnish (NFE) AF: 0.209 AC: 35177 AN: 168614

Other (OTH) AF: 0.248 AC: 4113 AN: 16578

GnomAD4 genome AF: 0.289 AC: 43889 AN: 151952 Hom.: 6793 Cov.: 32 AF XY: 0.294 AC XY: 21845 AN XY: 74274

African (AFR) AF: 0.398 AC: 16475 AN: 41440

American (AMR) AF: 0.288 AC: 4387 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 726 AN: 3472

East Asian (EAS) AF: 0.402 AC: 2068 AN: 5142

South Asian (SAS) AF: 0.267 AC: 1285 AN: 4816

European-Finnish (FIN) AF: 0.337 AC: 3551 AN: 10552

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.215 AC: 14602 AN: 67964

Other (OTH) AF: 0.284 AC: 599 AN: 2106

Alfa AF: 0.240 Hom.: 5217

Bravo AF: 0.295

Asia WGS AF: 0.333 AC: 1160 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Vanishing white matter disease Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.4
DANN	Benign	0.46
PhyloP100		-0.79
PromoterAI		-0.036	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2292611; hg19: chr3-183852861;