rs2292611

Positions:

• chr3-184135073-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NR_183718.1(EIF2B5-DT):​n.67+122T>C variant causes a intron, non coding transcript 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-DT NR_183718.1 intron, non_coding_transcript
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.787

Genes affected

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

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 -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 id 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/exons	MANE	UniProt
EIF2B5-DT	NR_183718.1	n.67+122T>C		intron_variant, non_coding_transcript_variant
EIF2B5-DT	NR_183721.1	n.189T>C		non_coding_transcript_exon_variant	1/2
EIF2B5-DT	NR_183719.1	n.67+122T>C		intron_variant, non_coding_transcript_variant
EIF2B5-DT	NR_183720.1	n.104+85T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EIF2B5-DT	ENST00000608135.1	n.44+122T>C		intron_variant, non_coding_transcript_variant		5
EIF2B5	ENST00000491144.5	n.36A>G		non_coding_transcript_exon_variant	1/15	2
EIF2B5-DT	ENST00000608232.5	n.24+85T>C		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR exome AF: 0.390

Gnomad4 AMR exome AF: 0.301

Gnomad4 ASJ exome AF: 0.202

Gnomad4 EAS exome AF: 0.409

Gnomad4 SAS exome AF: 0.260

Gnomad4 FIN exome AF: 0.323

Gnomad4 NFE exome AF: 0.209

Gnomad4 OTH exome AF: 0.248

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

Gnomad4 AFR AF: 0.398

Gnomad4 AMR AF: 0.288

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.402

Gnomad4 SAS AF: 0.267

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.215

Gnomad4 OTH AF: 0.284

Alfa AF: 0.228 Hom.: 3627

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Vanishing white matter disease Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.4
DANN	Benign	0.46

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2292611; hg19: chr3-183852861;