dbSNP rs201241803: EIF2S3B:p.Cys135Cys (chr12-10506307-T-C) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001357734.3(EIF2S3B):c.405T>C(p.Cys135Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000918 in 1,614,142 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00067 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00094 ( 8 hom. )

Consequence

EIF2S3B
NM_001357734.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.95

Publications

0 publications found

Variant links:

Genes affected

EIF2S3B (HGNC:43863): (eukaryotic translation initiation factor 2 subunit gamma B) Predicted to enable translation initiation factor activity. Predicted to contribute to tRNA binding activity. Predicted to be involved in formation of translation preinitiation complex and positive regulation of translational fidelity. Predicted to be part of eukaryotic translation initiation factor 2 complex. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

EIF2S3B links:

LOC105369657 (HGNC:):

LOC105369657 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 12-10506307-T-C is Benign according to our data. Variant chr12-10506307-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2642700.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.95 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 8 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001357734.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF2S3B	NM_001357734.3	MANE Select	c.405T>C	p.Cys135Cys	synonymous	Exon 1 of 1	NP_001344663.1	Q2VIR3-1
	EIF2S3B	NM_001357731.1		c.405T>C	p.Cys135Cys	synonymous	Exon 1 of 2	NP_001344660.1	Q2VIR3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF2S3B	ENST00000538173.2	TSL:6 MANE Select	c.405T>C	p.Cys135Cys	synonymous	Exon 1 of 1	ENSP00000445077.1	Q2VIR3-1
	EIF2S3B	ENST00000322446.3	TSL:1	c.405T>C	p.Cys135Cys	synonymous	Exon 1 of 2	ENSP00000323063.3	Q2VIR3-2

Frequencies

GnomAD3 genomes

AF:

0.000670

AC:

102

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00560

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000823

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.00125

AC:

315

AN:

251492

AF XY:

0.00167

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000809

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.000943

AC:

1379

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00116

AC XY:

847

AN XY:

727236

show subpopulations

African (AFR)

AF:

0.000149

AC:

AN:

33480

American (AMR)

AF:

0.000425

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00705

AC:

608

AN:

86258

European-Finnish (FIN)

AF:

0.0000374

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00191

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000611

AC:

679

AN:

1111984

Other (OTH)

AF:

0.000911

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

190

286

381

476

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<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:

0.000670

AC:

102

AN:

152278

Hom.:

Cov.:

AF XY:

0.000846

AC XY:

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

41560

American (AMR)

AF:

0.000719

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00560

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000823

AC:

AN:

68020

Other (OTH)

AF:

0.00142

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

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:

0.000753

Hom.:

Bravo

AF:

0.000544

EpiCase

AF:

0.000818

EpiControl

AF:

0.000948

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

8.5

(source)

DANN

Benign

0.56

PhyloP100

1.9

PromoterAI

0.017

Neutral

(source)

Mutation Taster

=100/0

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