Variant chr12-53016553-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001417.7(EIF4B):c.94A>G(p.Thr32Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000387 in 1,613,382 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00039 ( 2 hom. )

Consequence

EIF4B
NM_001417.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.32

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008408636).

BS2

High AC in GnomAd4 at 60 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
EIF4B	NM_001417.7 linkuse as main transcript	c.94A>G	p.Thr32Ala	missense_variant	2/15	ENST00000262056.14	NP_001408.2
EIF4B	NM_001300821.3 linkuse as main transcript	c.94A>G	p.Thr32Ala	missense_variant	2/15		NP_001287750.1
EIF4B	NM_001330654.2 linkuse as main transcript	c.94A>G	p.Thr32Ala	missense_variant	2/14		NP_001317583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF4B	ENST00000262056.14 linkuse as main transcript	c.94A>G	p.Thr32Ala	missense_variant	2/15	1	NM_001417.7	ENSP00000262056	P4	P23588-1
TNS2-AS1	ENST00000552905.6 linkuse as main transcript	n.321-1610T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000394

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00950

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000323

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000555

AC:

138

AN:

248586

Hom.:

AF XY:

0.000519

AC XY:

AN XY:

134886

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.000321

Gnomad ASJ exome

AF:

0.00907

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000266

Gnomad OTH exome

AF:

0.000828

GnomAD4 exome

AF:

0.000386

AC:

564

AN:

1461036

Hom.:

Cov.:

AF XY:

0.000374

AC XY:

272

AN XY:

726814

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000292

Gnomad4 ASJ exome

AF:

0.00931

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000230

Gnomad4 OTH exome

AF:

0.000746

GnomAD4 genome

AF:

0.000394

AC:

AN:

152346

Hom.:

Cov.:

AF XY:

0.000403

AC XY:

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00950

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000323

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000666

Hom.:

Bravo

AF:

0.000450

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000367

AC:

ExAC

AF:

0.000373

AC:

EpiCase

AF:

0.00104

EpiControl

AF:

0.000356

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

Jul 14, 2022

The c.94A>G (p.T32A) alteration is located in exon 2 (coding exon 2) of the EIF4B gene. This alteration results from a A to G substitution at nucleotide position 94, causing the threonine (T) at amino acid position 32 to be replaced by an alanine (A). 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

Benign

0.090

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.12

CADD

Benign

DANN

Benign

0.73

DEOGEN2

Benign

0.23

T;.;.;.;.

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.37

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.70

T;T;T;T;T

M_CAP

Benign

0.063

MetaRNN

Benign

0.0084

T;T;T;T;T

MetaSVM

Uncertain

-0.13

MutationAssessor

Uncertain

2.1

M;.;M;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.8

N;N;N;N;N

REVEL

Benign

0.29

Sift

Benign

0.13

T;T;T;T;T

Sift4G

Benign

0.23

T;T;T;T;T

Polyphen

0.077

B;B;.;.;.

Vest4

0.28

MVP

0.89

MPC

1.1

ClinPred

0.053

GERP RS

3.5

Varity_R

0.063

gMVP

0.27

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

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