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.

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.-7C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 22	NP_003741.1
	EIF3A	NM_003750.4	MANE Select	c.-7C>T		5_prime_UTR	Exon 1 of 22	NP_003741.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
EIF3A	ENST00000369144.8	TSL:1 MANE Select	c.-7C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 22	ENSP00000358140.3
EIF3A	ENST00000369144.8	TSL:1 MANE Select	c.-7C>T	5_prime_UTR	Exon 1 of 22	ENSP00000358140.3
EIF3A	ENST00000929552.1		c.-7C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 22	ENSP00000599611.1

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over