Genetic Variant EIF4E:c.540-10_540-8dupTTT (chr4-98881149-G-GAAA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001968.5(EIF4E):c.540-10_540-8dupTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 1,141,726 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

EIF4E
NM_001968.5 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.94

Variant links:

Genes affected

EIF4E (HGNC:3287): (eukaryotic translation initiation factor 4E) The protein encoded by this gene is a component of the eukaryotic translation initiation factor 4F complex, which recognizes the 7-methylguanosine cap structure at the 5' end of messenger RNAs. The encoded protein aids in translation initiation by recruiting ribosomes to the 5'-cap structure. Association of this protein with the 4F complex is the rate-limiting step in translation initiation. This gene acts as a proto-oncogene, and its expression and activation is associated with transformation and tumorigenesis. Several pseudogenes of this gene are found on other chromosomes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]

EIF4E links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
EIF4E	NM_001968.5 link	c.540-10_540-8dupTTT	splice_region_variant, intron_variant	Intron 6 of 6	ENST00000450253.7	NP_001959.1	P06730-1
EIF4E	NM_001130679.3 link	c.633-10_633-8dupTTT	splice_region_variant, intron_variant	Intron 7 of 7		NP_001124151.1	P06730-2
EIF4E	NM_001331017.2 link	c.624-10_624-8dupTTT	splice_region_variant, intron_variant	Intron 7 of 7		NP_001317946.1	P06730D6RBW1
EIF4E	NM_001130678.4 link	c.600-10_600-8dupTTT	splice_region_variant, intron_variant	Intron 6 of 6		NP_001124150.1	P06730-3Q32Q75X5D7E3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF4E	ENST00000450253.7 link	c.540-10_540-8dupTTT		splice_region_variant, intron_variant	Intron 6 of 6	1	NM_001968.5	ENSP00000389624.2		P06730-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000754

AC:

AN:

92850

AF XY:

0.0000607

show subpopulations

Gnomad AFR exome

AF:

0.000266

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000310

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000714

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000131

AC:

AN:

1141726

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

566568

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000375

AC:

AN:

26662

American (AMR)

AF:

0.00

AC:

AN:

31884

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19184

East Asian (EAS)

AF:

0.0000706

AC:

AN:

28330

South Asian (SAS)

AF:

0.0000314

AC:

AN:

63750

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39784

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4698

European-Non Finnish (NFE)

AF:

0.0000102

AC:

AN:

881092

Other (OTH)

AF:

0.0000216

AC:

AN:

46342

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.235

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

4-98881149-G-GAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over