dbSNP rs266719: EIF4A2:c.29+220T>C (chr3-186783859-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001967.4(EIF4A2):c.29+220T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.807 in 648,812 control chromosomes in the GnomAD database, including 212,250 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 0.83 ( 53276 hom., cov: 32)

Exomes 𝑓: 0.80 ( 158974 hom. )

Consequence

EIF4A2
NM_001967.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.12

Publications

18 publications found

Variant links:

Genes affected

EIF4A2 (HGNC:3284): (eukaryotic translation initiation factor 4A2) Enables ATP hydrolysis activity. Involved in negative regulation of RNA-directed 5'-3' RNA polymerase activity. Located in perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

EIF4A2 Gene-Disease associations (from GenCC):

neurodevelopmental disorder with hypotonia and speech delay, with or without seizures
Inheritance: AR, AD Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, G2P

EIF4A2 links:

ENSG00000263826 (HGNC:):

ENSG00000263826 links:

Genome browser will be placed here

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=-0.71).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF4A2	NM_001967.4 link	c.29+220T>C		intron_variant	Intron 1 of 10	ENST00000323963.10	NP_001958.2	Q14240-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF4A2	ENST00000323963.10 link	c.29+220T>C		intron_variant	Intron 1 of 10	1	NM_001967.4	ENSP00000326381.5		Q14240-1

Frequencies

GnomAD3 genomes

AF:

0.834

AC:

126799

AN:

152064

Hom.:

53215

Cov.:

show subpopulations

Gnomad AFR

AF:

0.926

Gnomad AMI

AF:

0.802

Gnomad AMR

AF:

0.833

Gnomad ASJ

AF:

0.765

Gnomad EAS

AF:

0.903

Gnomad SAS

AF:

0.784

Gnomad FIN

AF:

0.841

Gnomad MID

AF:

0.816

Gnomad NFE

AF:

0.779

Gnomad OTH

AF:

0.820

GnomAD4 exome

AF:

0.799

AC:

396741

AN:

496630

Hom.:

158974

Cov.:

AF XY:

0.798

AC XY:

206924

AN XY:

259464

show subpopulations

African (AFR)

AF:

0.927

AC:

12386

AN:

13356

American (AMR)

AF:

0.820

AC:

15448

AN:

18846

Ashkenazi Jewish (ASJ)

AF:

0.760

AC:

10484

AN:

13788

East Asian (EAS)

AF:

0.924

AC:

28730

AN:

31094

South Asian (SAS)

AF:

0.769

AC:

34531

AN:

44876

European-Finnish (FIN)

AF:

0.839

AC:

26879

AN:

32036

Middle Eastern (MID)

AF:

0.832

AC:

1693

AN:

2036

European-Non Finnish (NFE)

AF:

0.781

AC:

244587

AN:

313266

Other (OTH)

AF:

0.805

AC:

22003

AN:

27332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

3805

7611

11416

15222

19027

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2072

4144

6216

8288

10360

<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:

0.834

AC:

126919

AN:

152182

Hom.:

53276

Cov.:

AF XY:

0.835

AC XY:

62120

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.926

AC:

38449

AN:

41518

American (AMR)

AF:

0.834

AC:

12751

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.765

AC:

2656

AN:

3472

East Asian (EAS)

AF:

0.902

AC:

4659

AN:

5164

South Asian (SAS)

AF:

0.784

AC:

3780

AN:

4824

European-Finnish (FIN)

AF:

0.841

AC:

8911

AN:

10594

Middle Eastern (MID)

AF:

0.827

AC:

243

AN:

294

European-Non Finnish (NFE)

AF:

0.779

AC:

52999

AN:

67994

Other (OTH)

AF:

0.822

AC:

1740

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1066

2132

3199

4265

5331

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

884

1768

2652

3536

4420

<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:

0.796

Hom.:

91617

Bravo

AF:

0.835

Asia WGS

AF:

0.869

AC:

3020

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

2.4

(source)

DANN

Benign

0.44

PhyloP100

-1.1

PromoterAI

0.014

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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