5-176645867-C-G

Position:

• chr5-176645867-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001099408.2(EIF4E1B):​c.616C>G​(p.Arg206Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EIF4E1B NM_001099408.2 missense, splice_region
• Scores: Splicing: ADA: 0.08614
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.28

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF4E1B	NM_001099408.2	c.616C>G	p.Arg206Gly	missense_variant, splice_region_variant	9/9	ENST00000318682.11	NP_001092878.1
EIF4E1B	NM_001375362.1	c.616C>G	p.Arg206Gly	missense_variant, splice_region_variant	9/9		NP_001362291.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF4E1B	ENST00000318682.11	c.616C>G	p.Arg206Gly	missense_variant, splice_region_variant	9/9	5	NM_001099408.2	ENSP00000323714	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 17, 2022

The c.616C>G (p.R206G) alteration is located in exon 9 (coding exon 7) of the EIF4E1B gene. This alteration results from a C to G substitution at nucleotide position 616, causing the arginine (R) at amino acid position 206 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T;T;T
Eigen	Benign	0.093
Eigen_PC	Benign	0.017
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.94	.;D;.
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.58	D;D;D
MetaSVM	Benign	-0.75	T
MutationAssessor	Uncertain	2.3	M;M;M
MutationTaster	Benign	0.88	N;N
PrimateAI	Benign	0.18	T
PROVEAN	Pathogenic	-5.2	.;D;D
REVEL	Benign	0.20
Sift	Benign	0.054	.;T;T
Sift4G	Uncertain	0.049	.;D;D
Polyphen		0.56	P;P;P
Vest4		0.43, 0.43
MutPred		0.61		Loss of MoRF binding (P = 0.0249);Loss of MoRF binding (P = 0.0249);Loss of MoRF binding (P = 0.0249);
MVP		0.67
MPC		0.82
ClinPred		0.91	D
GERP RS		4.1
Varity_R		0.33
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.086
dbscSNV1_RF	Benign	0.16
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-176072868;