Genetic Variant EIF3A:c.742-138C>T (chr10-119069792-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003750.4(EIF3A):c.742-138C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0417 in 607,670 control chromosomes in the GnomAD database, including 1,273 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.073 ( 816 hom., cov: 33)

Exomes 𝑓: 0.031 ( 457 hom. )

Consequence

EIF3A
NM_003750.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.369

Publications

1 publications found

Variant links:

Genes affected

EIF3A (HGNC:3271): (eukaryotic translation initiation factor 3 subunit A) Enables RNA binding activity. Contributes to translation initiation factor activity. Involved in IRES-dependent viral translational initiation; formation of cytoplasmic translation initiation complex; and viral translational termination-reinitiation. Located in cytosol; nucleolus; and nucleoplasm. Part of eukaryotic translation initiation factor 3 complex. [provided by Alliance of Genome Resources, Apr 2022]

EIF3A links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003750.4. 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
	EIF3A	NM_003750.4	MANE Select	c.742-138C>T		intron	N/A	NP_003741.1	Q14152-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EIF3A	ENST00000369144.8	TSL:1 MANE Select	c.742-138C>T	intron	N/A	ENSP00000358140.3	Q14152-1
EIF3A	ENST00000929552.1		c.742-138C>T	intron	N/A	ENSP00000599611.1
EIF3A	ENST00000947789.1		c.742-138C>T	intron	N/A	ENSP00000617848.1

Frequencies

GnomAD3 genomes

AF:

0.0729

AC:

11093

AN:

152064

Hom.:

814

Cov.:

show subpopulations

Gnomad AFR

AF:

0.192

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0413

Gnomad ASJ

AF:

0.0110

Gnomad EAS

AF:

0.0518

Gnomad SAS

AF:

0.0103

Gnomad FIN

AF:

0.0109

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0281

Gnomad OTH

AF:

0.0630

GnomAD4 exome

AF:

0.0312

AC:

14220

AN:

455488

Hom.:

457

AF XY:

0.0295

AC XY:

7162

AN XY:

242496

show subpopulations

African (AFR)

AF:

0.190

AC:

2376

AN:

12498

American (AMR)

AF:

0.0320

AC:

585

AN:

18300

Ashkenazi Jewish (ASJ)

AF:

0.0123

AC:

169

AN:

13750

East Asian (EAS)

AF:

0.0600

AC:

1873

AN:

31196

South Asian (SAS)

AF:

0.00984

AC:

440

AN:

44702

European-Finnish (FIN)

AF:

0.0124

AC:

371

AN:

29832

Middle Eastern (MID)

AF:

0.0292

AC:

AN:

1986

European-Non Finnish (NFE)

AF:

0.0266

AC:

7361

AN:

276948

Other (OTH)

AF:

0.0376

AC:

987

AN:

26276

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

646

1293

1939

2586

3232

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

168

252

336

420

<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:

0.0730

AC:

11111

AN:

152182

Hom.:

816

Cov.:

AF XY:

0.0702

AC XY:

5224

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.191

AC:

7940

AN:

41486

American (AMR)

AF:

0.0413

AC:

631

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0110

AC:

AN:

3470

East Asian (EAS)

AF:

0.0517

AC:

268

AN:

5186

South Asian (SAS)

AF:

0.0104

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0109

AC:

115

AN:

10594

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0281

AC:

1910

AN:

68014

Other (OTH)

AF:

0.0629

AC:

133

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

475

949

1424

1898

2373

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

224

336

448

560

<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:

0.0431

Hom.:

103

Bravo

AF:

0.0812

Asia WGS

AF:

0.0420

AC:

146

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

5.0

(source)

DANN

Benign

0.36

PhyloP100

-0.37

Mutation Taster

=100/0

polymorphism (auto)

(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

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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