5-176645226-C-G

Variant names:

• chr5-176645226-C-G
• rs762675292
• NM_001099408.2:c.457C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001099408.2(EIF4E1B):​c.457C>G​(p.Arg153Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000693 in 1,442,724 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R153W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: EIF4E1B NM_001099408.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.89
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.457C>G	p.Arg153Gly	missense	Exon 7 of 9	NP_001092878.1	A6NMX2
	EIF4E1B	NM_001375362.1		c.457C>G	p.Arg153Gly	missense	Exon 7 of 9	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.457C>G	p.Arg153Gly	missense	Exon 7 of 9	ENSP00000323714.6	A6NMX2
	EIF4E1B	ENST00000504597.5	TSL:5	c.457C>G	p.Arg153Gly	missense	Exon 7 of 9	ENSP00000427633.1	A6NMX2
	EIF4E1B	ENST00000647833.1		c.457C>G	p.Arg153Gly	missense	Exon 8 of 10	ENSP00000497422.1	A6NMX2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.93e-7 AC: 1 AN: 1442724 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 716060

African (AFR) AF: 0.00 AC: 0 AN: 33068

American (AMR) AF: 0.00 AC: 0 AN: 41094

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25746

East Asian (EAS) AF: 0.00 AC: 0 AN: 38652

South Asian (SAS) AF: 0.00 AC: 0 AN: 83774

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51996

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 9.07e-7 AC: 1 AN: 1102970

Other (OTH) AF: 0.00 AC: 0 AN: 59684

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.0097	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.051	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Benign	-0.34	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		3.9
PrimateAI	Benign	0.21	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Benign	0.21
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.037	D
Polyphen		0.39	B
Vest4		0.67
MutPred		0.63		Loss of MoRF binding (P = 0.0683)
MVP		0.65
MPC		0.69
ClinPred		0.98	D
GERP RS		4.9
Varity_R		0.33
gMVP		0.41
Mutation Taster		=61/39	polymorphism

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

Other links and lift over

dbSNP: rs762675292; hg19: chr5-176072227;