dbSNP rs3740556: EIF3A:c.-7C>T (chr10-119080683-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_003750.4(EIF3A):c.-7C>T variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.00022 in 1,592,550 control chromosomes in the GnomAD database, including 1 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 0.00024 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00022 ( 1 hom. )

Consequence

EIF3A
NM_003750.4 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.20

Publications

7 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:

ENSG00000289126 (HGNC:):

ENSG00000289126 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BS2

High AC in GnomAd4 at 36 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF3A	NM_003750.4 link	c.-7C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 22	ENST00000369144.8	NP_003741.1	Q14152-1
EIF3A	NM_003750.4 link	c.-7C>T		5_prime_UTR_variant	Exon 1 of 22	ENST00000369144.8	NP_003741.1	Q14152-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
EIF3A	ENST00000369144.8 link	c.-7C>T	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 22	1	NM_003750.4	ENSP00000358140.3	Q14152-1
EIF3A	ENST00000369144.8 link	c.-7C>T	5_prime_UTR_variant	Exon 1 of 22	1	NM_003750.4	ENSP00000358140.3	Q14152-1
ENSG00000289126	ENST00000687829.3 link	n.-211G>A	upstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.000237

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00693

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000705

AC:

149

AN:

211466

AF XY:

0.000679

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00939

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000218

AC:

314

AN:

1440226

Hom.:

Cov.:

AF XY:

0.000204

AC XY:

146

AN XY:

714740

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32068

American (AMR)

AF:

0.00

AC:

AN:

41552

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25620

East Asian (EAS)

AF:

0.00766

AC:

295

AN:

38532

South Asian (SAS)

AF:

0.0000241

AC:

AN:

82834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51492

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5732

European-Non Finnish (NFE)

AF:

0.00000363

AC:

AN:

1102830

Other (OTH)

AF:

0.000218

AC:

AN:

59566

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

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:

0.000236

AC:

AN:

152324

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41578

American (AMR)

AF:

0.00

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00696

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68012

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

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:

0.000880

Hom.:

Bravo

AF:

0.000287

Asia WGS

AF:

0.00144

AC:

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.79

PhyloP100

4.2

PromoterAI

-0.061

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

Mutation Taster

=292/8

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over