rs182336246

Variant names:

• chr5-176645867-C-G
• rs182336246
• NM_001099408.2:c.616C>G

Your query was ambiguous. Multiple possible variants found:

• chr5-176645867-C-G
• chr5-176645867-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R206L) has been classified 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
• 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.616C>G	p.Arg206Gly	missense splice_region	Exon 9 of 9	NP_001092878.1	A6NMX2
	EIF4E1B	NM_001375362.1		c.616C>G	p.Arg206Gly	missense splice_region	Exon 9 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.616C>G	p.Arg206Gly	missense splice_region	Exon 9 of 9	ENSP00000323714.6	A6NMX2
	EIF4E1B	ENST00000504597.5	TSL:5	c.616C>G	p.Arg206Gly	missense splice_region	Exon 9 of 9	ENSP00000427633.1	A6NMX2
	EIF4E1B	ENST00000647833.1		c.616C>G	p.Arg206Gly	missense splice_region	Exon 10 of 10	ENSP00000497422.1	A6NMX2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
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
MetaSVM	Benign	-0.75	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		1.3
PrimateAI	Benign	0.18	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Benign	0.20
Sift	Benign	0.054	T
Sift4G	Uncertain	0.049	D
Polyphen		0.56	P
Vest4		0.43
MutPred		0.61		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
Mutation Taster		=70/30	polymorphism

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

Other links and lift over

dbSNP: rs182336246; hg19: chr5-176072868;