5-176643197-CT-TC

Variant names:

• chr5-176643197-CT-TC
• NM_001099408.2:c.131_132delCTinsTC
• EIF4E1B p.Ser44Phe

Variant summary

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

The NM_001099408.2(EIF4E1B):​c.131_132delCTinsTC​(p.Ser44Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: EIF4E1B NM_001099408.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.516
• Publications: 0 publications found

Genes affected

EIF4E1B (HGNC:33179): (eukaryotic translation initiation factor 4E family member 1B) Predicted to enable RNA 7-methylguanosine cap binding activity and translation initiation factor activity. Predicted to be involved in regulation of translation and translational initiation. Predicted to be located in cytoplasm. Predicted to be part of eukaryotic translation initiation factor 4F complex and mRNA cap binding activity complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099408.2. 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
	EIF4E1B	NM_001099408.2	MANE Select	c.131_132delCTinsTC	p.Ser44Phe	missense	N/A	NP_001092878.1	A6NMX2
	EIF4E1B	NM_001375362.1		c.131_132delCTinsTC	p.Ser44Phe	missense	N/A	NP_001362291.1	A6NMX2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF4E1B	ENST00000318682.11	TSL:5 MANE Select	c.131_132delCTinsTC	p.Ser44Phe	missense	N/A	ENSP00000323714.6	A6NMX2
	EIF4E1B	ENST00000504597.5	TSL:5	c.131_132delCTinsTC	p.Ser44Phe	missense	N/A	ENSP00000427633.1	A6NMX2
	EIF4E1B	ENST00000647833.1		c.131_132delCTinsTC	p.Ser44Phe	missense	N/A	ENSP00000497422.1	A6NMX2

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.52

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr5-176070198;