dbSNP rs11899983: EIF4E2:c.20+524T>C (chr2-232551268-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_004846.4(EIF4E2):c.20+524T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 471,858 control chromosomes in the GnomAD database, including 78,362 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 0.58 ( 25707 hom., cov: 30)

Exomes 𝑓: 0.57 ( 52655 hom. )

Consequence

EIF4E2
NM_004846.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0640

Publications

8 publications found

Variant links:

Genes affected

EIF4E2 (HGNC:3293): (eukaryotic translation initiation factor 4E family member 2) Enables ubiquitin protein ligase binding activity. Involved in positive regulation of miRNA mediated inhibition of translation. Acts upstream of or within negative regulation of translation. Located in P-body. Part of mRNA cap binding activity complex. [provided by Alliance of Genome Resources, Apr 2022]

EIF4E2 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=-0.8).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF4E2	NM_004846.4 link	c.20+524T>C		intron_variant	Intron 1 of 6	ENST00000258416.8	NP_004837.1	O60573-1Q53RG0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF4E2	ENST00000258416.8 link	c.20+524T>C		intron_variant	Intron 1 of 6	1	NM_004846.4	ENSP00000258416.3		O60573-1

Frequencies

GnomAD3 genomes

AF:

0.579

AC:

87863

AN:

151792

Hom.:

25670

Cov.:

show subpopulations

Gnomad AFR

AF:

0.596

Gnomad AMI

AF:

0.756

Gnomad AMR

AF:

0.652

Gnomad ASJ

AF:

0.557

Gnomad EAS

AF:

0.553

Gnomad SAS

AF:

0.548

Gnomad FIN

AF:

0.515

Gnomad MID

AF:

0.535

Gnomad NFE

AF:

0.565

Gnomad OTH

AF:

0.594

GnomAD2 exomes

AF:

0.582

AC:

86881

AN:

149252

AF XY:

0.576

show subpopulations

Gnomad AFR exome

AF:

0.595

Gnomad AMR exome

AF:

0.696

Gnomad ASJ exome

AF:

0.566

Gnomad EAS exome

AF:

0.556

Gnomad FIN exome

AF:

0.529

Gnomad NFE exome

AF:

0.568

Gnomad OTH exome

AF:

0.587

GnomAD4 exome

AF:

0.570

AC:

182437

AN:

319946

Hom.:

52655

Cov.:

AF XY:

0.567

AC XY:

102501

AN XY:

180720

show subpopulations

African (AFR)

AF:

0.594

AC:

5167

AN:

8696

American (AMR)

AF:

0.698

AC:

19080

AN:

27318

Ashkenazi Jewish (ASJ)

AF:

0.565

AC:

6136

AN:

10860

East Asian (EAS)

AF:

0.556

AC:

5140

AN:

9248

South Asian (SAS)

AF:

0.546

AC:

32626

AN:

59746

European-Finnish (FIN)

AF:

0.526

AC:

14248

AN:

27096

Middle Eastern (MID)

AF:

0.563

AC:

1571

AN:

2788

European-Non Finnish (NFE)

AF:

0.565

AC:

90307

AN:

159782

Other (OTH)

AF:

0.566

AC:

8162

AN:

14412

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

4797

9593

14390

19186

23983

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

542

1084

1626

2168

2710

<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:

0.579

AC:

87950

AN:

151912

Hom.:

25707

Cov.:

AF XY:

0.576

AC XY:

42735

AN XY:

74220

show subpopulations

African (AFR)

AF:

0.596

AC:

24663

AN:

41388

American (AMR)

AF:

0.653

AC:

9975

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.557

AC:

1932

AN:

3468

East Asian (EAS)

AF:

0.551

AC:

2842

AN:

5156

South Asian (SAS)

AF:

0.548

AC:

2636

AN:

4812

European-Finnish (FIN)

AF:

0.515

AC:

5429

AN:

10540

Middle Eastern (MID)

AF:

0.544

AC:

160

AN:

294

European-Non Finnish (NFE)

AF:

0.565

AC:

38370

AN:

67950

Other (OTH)

AF:

0.595

AC:

1257

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1865

3731

5596

7462

9327

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

742

1484

2226

2968

3710

<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:

0.574

Hom.:

44236

Bravo

AF:

0.597

Asia WGS

AF:

0.608

AC:

2117

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

6.5

(source)

DANN

Benign

0.80

PhyloP100

0.064

PromoterAI

-0.026

Neutral

(source)

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over