Genetic Variant NM_001037283.2:c.208C>T (chr7-2355129-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001037283.2(EIF3B):c.208C>T(p.Pro70Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000235 in 1,403,096 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

EIF3B
NM_001037283.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.326

Publications

0 publications found

Variant links:

Genes affected

EIF3B (HGNC:3280): (eukaryotic translation initiation factor 3 subunit B) Enables RNA binding activity. Contributes to translation initiation factor activity. Involved in several processes, including IRES-dependent viral translational initiation; translational initiation; and viral translational termination-reinitiation. Located in extracellular exosome. Part of eukaryotic translation initiation factor 3 complex. [provided by Alliance of Genome Resources, Apr 2022]

EIF3B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06706062).

BS2

High AC in GnomAdExome4 at 31 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001037283.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EIF3B	NM_001037283.2	MANE Select	c.208C>T	p.Pro70Ser	missense	Exon 1 of 19	NP_001032360.1	P55884-1
EIF3B	NM_001362791.2		c.208C>T	p.Pro70Ser	missense	Exon 1 of 19	NP_001349720.1	P55884-1
EIF3B	NM_003751.4		c.208C>T	p.Pro70Ser	missense	Exon 1 of 19	NP_003742.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EIF3B	ENST00000360876.9	TSL:1 MANE Select	c.208C>T	p.Pro70Ser	missense	Exon 1 of 19	ENSP00000354125.4	P55884-1
EIF3B	ENST00000397011.2	TSL:1	c.208C>T	p.Pro70Ser	missense	Exon 1 of 19	ENSP00000380206.2	P55884-1
EIF3B	ENST00000899983.1		c.208C>T	p.Pro70Ser	missense	Exon 1 of 19	ENSP00000570042.1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151478

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000444

AC:

AN:

22514

AF XY:

0.00

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:

0.000674

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000248

AC:

AN:

1251618

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

613694

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24444

American (AMR)

AF:

0.00

AC:

AN:

13574

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18476

East Asian (EAS)

AF:

0.00

AC:

AN:

27822

South Asian (SAS)

AF:

0.0000163

AC:

AN:

61368

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3608

European-Non Finnish (NFE)

AF:

0.0000265

AC:

AN:

1020246

Other (OTH)

AF:

0.0000581

AC:

AN:

51666

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

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

AF:

0.0000132

AC:

AN:

151478

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73978

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41300

American (AMR)

AF:

0.0000657

AC:

AN:

15230

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5118

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10490

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67758

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000227

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

Benign

0.077

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.022

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.0056

LIST_S2

Benign

0.47

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.067

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PhyloP100

0.33

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.10

REVEL

Benign

0.033

Sift

Benign

0.042

Sift4G

Benign

0.15

Polyphen

0.0

Vest4

0.064

MutPred

0.27

Gain of phosphorylation at P70 (P = 0.0017)

MVP

0.17

MPC

0.38

ClinPred

0.055

GERP RS

2.3

PromoterAI

-0.0048

Neutral

(source)

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

3.5

Varity_R

0.040

gMVP

0.22

Mutation Taster

=97/3

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over