Genetic Variant EIF3A:c.378-110T>A (chr10-119073163-A-T) – 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.378-110T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.942 in 1,057,278 control chromosomes in the GnomAD database, including 474,965 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 0.85 ( 57351 hom., cov: 33)

Exomes 𝑓: 0.96 ( 417614 hom. )

Consequence

EIF3A
NM_003750.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.00

Publications

10 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=-0.97).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.965 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.378-110T>A		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.378-110T>A	intron	N/A	ENSP00000358140.3	Q14152-1
EIF3A	ENST00000929552.1		c.378-110T>A	intron	N/A	ENSP00000599611.1
EIF3A	ENST00000947789.1		c.378-110T>A	intron	N/A	ENSP00000617848.1

Frequencies

GnomAD3 genomes

AF:

0.847

AC:

128849

AN:

152126

Hom.:

57342

Cov.:

show subpopulations

Gnomad AFR

AF:

0.541

Gnomad AMI

AF:

0.985

Gnomad AMR

AF:

0.931

Gnomad ASJ

AF:

0.982

Gnomad EAS

AF:

0.883

Gnomad SAS

AF:

0.957

Gnomad FIN

AF:

0.989

Gnomad MID

AF:

0.927

Gnomad NFE

AF:

0.971

Gnomad OTH

AF:

0.886

GnomAD4 exome

AF:

0.958

AC:

867174

AN:

905036

Hom.:

417614

AF XY:

0.959

AC XY:

437331

AN XY:

455942

show subpopulations

African (AFR)

AF:

0.537

AC:

10946

AN:

20384

American (AMR)

AF:

0.949

AC:

19911

AN:

20972

Ashkenazi Jewish (ASJ)

AF:

0.981

AC:

16617

AN:

16936

East Asian (EAS)

AF:

0.882

AC:

29621

AN:

33578

South Asian (SAS)

AF:

0.964

AC:

53869

AN:

55896

European-Finnish (FIN)

AF:

0.987

AC:

33393

AN:

33824

Middle Eastern (MID)

AF:

0.953

AC:

2915

AN:

3058

European-Non Finnish (NFE)

AF:

0.973

AC:

661300

AN:

679330

Other (OTH)

AF:

0.940

AC:

38602

AN:

41058

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1556

3111

4667

6222

7778

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11330

22660

33990

45320

56650

<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:

0.847

AC:

128895

AN:

152242

Hom.:

57351

Cov.:

AF XY:

0.851

AC XY:

63374

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.541

AC:

22447

AN:

41486

American (AMR)

AF:

0.931

AC:

14244

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.982

AC:

3409

AN:

3472

East Asian (EAS)

AF:

0.882

AC:

4570

AN:

5180

South Asian (SAS)

AF:

0.958

AC:

4625

AN:

4828

European-Finnish (FIN)

AF:

0.989

AC:

10505

AN:

10620

Middle Eastern (MID)

AF:

0.922

AC:

271

AN:

294

European-Non Finnish (NFE)

AF:

0.971

AC:

66053

AN:

68036

Other (OTH)

AF:

0.887

AC:

1873

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

753

1505

2258

3010

3763

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

866

1732

2598

3464

4330

<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:

0.902

Hom.:

7932

Bravo

AF:

0.829

Asia WGS

AF:

0.893

AC:

3106

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.084

(source)

DANN

Benign

0.38

PhyloP100

-2.0

Mutation Taster

=11/89

disease causing

(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