dbSNP rs1397617: EIF3A:c.377+149G>A (chr10-119073292-C-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.377+149G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 697,696 control chromosomes in the GnomAD database, including 109,591 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 0.51 ( 20809 hom., cov: 33)

Exomes 𝑓: 0.57 ( 88782 hom. )

Consequence

EIF3A
NM_003750.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.275

Publications

2 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=-0.84).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.628 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.377+149G>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.377+149G>A	intron	N/A	ENSP00000358140.3	Q14152-1
EIF3A	ENST00000929552.1		c.377+149G>A	intron	N/A	ENSP00000599611.1
EIF3A	ENST00000947789.1		c.377+149G>A	intron	N/A	ENSP00000617848.1

Frequencies

GnomAD3 genomes

AF:

0.506

AC:

76904

AN:

151894

Hom.:

20803

Cov.:

show subpopulations

Gnomad AFR

AF:

0.307

Gnomad AMI

AF:

0.719

Gnomad AMR

AF:

0.598

Gnomad ASJ

AF:

0.655

Gnomad EAS

AF:

0.491

Gnomad SAS

AF:

0.647

Gnomad FIN

AF:

0.612

Gnomad MID

AF:

0.677

Gnomad NFE

AF:

0.569

Gnomad OTH

AF:

0.568

GnomAD4 exome

AF:

0.566

AC:

309123

AN:

545684

Hom.:

88782

AF XY:

0.570

AC XY:

161018

AN XY:

282476

show subpopulations

African (AFR)

AF:

0.307

AC:

4363

AN:

14214

American (AMR)

AF:

0.591

AC:

9907

AN:

16774

Ashkenazi Jewish (ASJ)

AF:

0.660

AC:

9279

AN:

14066

East Asian (EAS)

AF:

0.536

AC:

16988

AN:

31716

South Asian (SAS)

AF:

0.646

AC:

27374

AN:

42368

European-Finnish (FIN)

AF:

0.599

AC:

19227

AN:

32108

Middle Eastern (MID)

AF:

0.716

AC:

1528

AN:

2134

European-Non Finnish (NFE)

AF:

0.562

AC:

204050

AN:

363316

Other (OTH)

AF:

0.566

AC:

16407

AN:

28988

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

6588

13175

19763

26350

32938

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2756

5512

8268

11024

13780

<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:

0.506

AC:

76926

AN:

152012

Hom.:

20809

Cov.:

AF XY:

0.513

AC XY:

38102

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.306

AC:

12699

AN:

41472

American (AMR)

AF:

0.599

AC:

9137

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.655

AC:

2274

AN:

3470

East Asian (EAS)

AF:

0.491

AC:

2549

AN:

5188

South Asian (SAS)

AF:

0.647

AC:

3119

AN:

4818

European-Finnish (FIN)

AF:

0.612

AC:

6446

AN:

10540

Middle Eastern (MID)

AF:

0.670

AC:

197

AN:

294

European-Non Finnish (NFE)

AF:

0.569

AC:

38655

AN:

67950

Other (OTH)

AF:

0.568

AC:

1197

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1855

3710

5565

7420

9275

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

682

1364

2046

2728

3410

<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:

0.522

Hom.:

2801

Bravo

AF:

0.494

Asia WGS

AF:

0.570

AC:

1979

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.4

(source)

DANN

Benign

0.27

PhyloP100

-0.28

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