Genetic Variant NM_001417.7:c.637C>A (chr12-53022597-C-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_ModerateBS2

The NM_001417.7(EIF4B):c.637C>A(p.Pro213Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,670 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: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

EIF4B
NM_001417.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.20

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2569578).

BS2

High AC in GnomAdExome4 at 5 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001417.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EIF4B	NM_001417.7	MANE Select	c.637C>A	p.Pro213Thr	missense	Exon 6 of 15	NP_001408.2	P23588-1
EIF4B	NM_001300821.3		c.637C>A	p.Pro213Thr	missense	Exon 6 of 15	NP_001287750.1	E7EX17
EIF4B	NM_001330654.2		c.520C>A	p.Pro174Thr	missense	Exon 5 of 14	NP_001317583.1	P23588-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EIF4B	ENST00000262056.14	TSL:1 MANE Select	c.637C>A	p.Pro213Thr	missense	Exon 6 of 15	ENSP00000262056.9	P23588-1
EIF4B	ENST00000961691.1		c.637C>A	p.Pro213Thr	missense	Exon 6 of 15	ENSP00000631750.1
EIF4B	ENST00000961687.1		c.637C>A	p.Pro213Thr	missense	Exon 6 of 15	ENSP00000631746.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000401

AC:

AN:

249232

AF XY:

0.00000740

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461670

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727144

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33474

American (AMR)

AF:

0.00

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5708

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1111896

Other (OTH)

AF:

0.0000166

AC:

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Benign

-0.062

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.56

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.22

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.0082

MetaRNN

Benign

0.26

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.0

PhyloP100

7.2

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.093

Sift

Uncertain

0.014

Sift4G

Benign

0.14

Polyphen

0.11

Vest4

0.59

MutPred

0.30

Gain of phosphorylation at P213 (P = 0.002)

MVP

0.38

MPC

1.7

ClinPred

0.91

GERP RS

2.7

Varity_R

0.13

gMVP

0.53

Mutation Taster

=88/12

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over