Variant 12-53027788-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The ENST00000262056.14(EIF4B):c.674G>A(p.Arg225Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000685 in 1,460,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

EIF4B
ENST00000262056.14 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.14

Variant links:

Genes affected

EIF4B (HGNC:3285): (eukaryotic translation initiation factor 4B) Enables RNA binding activity. Predicted to be involved in eukaryotic translation initiation factor 4F complex assembly and formation of translation preinitiation complex. Located in cytosol. Biomarker of autism spectrum disorder and major depressive disorder. [provided by Alliance of Genome Resources, Apr 2022]

EIF4B links:

TNS2-AS1 (HGNC:27464): (TNS2 antisense RNA 1)

TNS2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.26578552).

BS2

High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
EIF4B	NM_001417.7 linkuse as main transcript	c.674G>A	p.Arg225Gln	missense_variant	7/15	ENST00000262056.14	NP_001408.2
EIF4B	NM_001300821.3 linkuse as main transcript	c.674G>A	p.Arg225Gln	missense_variant	7/15		NP_001287750.1
EIF4B	NM_001330654.2 linkuse as main transcript	c.557G>A	p.Arg186Gln	missense_variant	6/14		NP_001317583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF4B	ENST00000262056.14 linkuse as main transcript	c.674G>A	p.Arg225Gln	missense_variant	7/15	1	NM_001417.7	ENSP00000262056	P4	P23588-1
TNS2-AS1	ENST00000552905.6 linkuse as main transcript	n.321-12845C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000810

AC:

AN:

246816

Hom.:

AF XY:

0.00000746

AC XY:

AN XY:

134126

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000181

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000685

AC:

AN:

1460742

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

726704

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000809

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000468

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 29, 2022

The c.674G>A (p.R225Q) alteration is located in exon 7 (coding exon 7) of the EIF4B gene. This alteration results from a G to A substitution at nucleotide position 674, causing the arginine (R) at amino acid position 225 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.75

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

0.0

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.36

T;.;.;.

Eigen

Benign

0.053

Eigen_PC

Benign

0.13

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.29

T;T;T;T

M_CAP

Uncertain

0.088

MetaRNN

Benign

0.27

T;T;T;T

MetaSVM

Uncertain

-0.036

MutationAssessor

Benign

1.5

L;.;.;.

MutationTaster

Benign

0.82

D;D;N

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-2.0

N;N;N;N

REVEL

Benign

0.24

Sift

Uncertain

0.014

D;D;D;T

Sift4G

Benign

0.12

T;T;T;T

Polyphen

0.80

P;P;.;.

Vest4

0.54

MutPred

0.34

Loss of MoRF binding (P = 0.0644);Loss of MoRF binding (P = 0.0644);.;.;

MVP

0.87

MPC

1.3

ClinPred

0.73

GERP RS

3.1

Varity_R

0.17

gMVP

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over