chr3-184135073-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.787
Variant links:
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]

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ACMG classification

Classification made for transcript

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-DTNR_183718.1 linkuse as main transcriptn.67+122T>C intron_variant, non_coding_transcript_variant
EIF2B5-DTNR_183721.1 linkuse as main transcriptn.189T>C non_coding_transcript_exon_variant 1/2
EIF2B5-DTNR_183719.1 linkuse as main transcriptn.67+122T>C intron_variant, non_coding_transcript_variant
EIF2B5-DTNR_183720.1 linkuse as main transcriptn.104+85T>C intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EIF2B5-DTENST00000608135.1 linkuse as main transcriptn.44+122T>C intron_variant, non_coding_transcript_variant 5
EIF2B5ENST00000491144.5 linkuse as main transcriptn.36A>G non_coding_transcript_exon_variant 1/152
EIF2B5-DTENST00000608232.5 linkuse as main transcriptn.24+85T>C intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
AF:
0.289
AC:
43844
AN:
151834
Hom.:
6788
Cov.:
32
show subpopulations
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
show subpopulations
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
show subpopulations
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:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxNov 11, 2018- -
Vanishing white matter disease Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2292611; hg19: chr3-183852861; API