rs770398185

Variant names:

• chr5-176645391-C-G
• rs770398185
• NM_001099408.2:c.489C>G

Your query was ambiguous. Multiple possible variants found:

• chr5-176645391-C-G
• chr5-176645391-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.489C>G​(p.Ile163Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,376,482 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. I163I) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: EIF4E1B NM_001099408.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.35
• 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.489C>G	p.Ile163Met	missense	Exon 8 of 9	NP_001092878.1	A6NMX2
	EIF4E1B	NM_001375362.1		c.489C>G	p.Ile163Met	missense	Exon 8 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.489C>G	p.Ile163Met	missense	Exon 8 of 9	ENSP00000323714.6	A6NMX2
	EIF4E1B	ENST00000504597.5	TSL:5	c.489C>G	p.Ile163Met	missense	Exon 8 of 9	ENSP00000427633.1	A6NMX2
	EIF4E1B	ENST00000647833.1		c.489C>G	p.Ile163Met	missense	Exon 9 of 10	ENSP00000497422.1	A6NMX2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000537 AC: 1 AN: 186070 AF XY: 0.0000101

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000626

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000145 AC: 2 AN: 1376482 Hom.: 0 Cov.: 31 AF XY: 0.00000296 AC XY: 2 AN XY: 674598

African (AFR) AF: 0.00 AC: 0 AN: 30848

American (AMR) AF: 0.00 AC: 0 AN: 32964

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20752

East Asian (EAS) AF: 0.00 AC: 0 AN: 38622

South Asian (SAS) AF: 0.0000275 AC: 2 AN: 72854

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5380

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1067768

Other (OTH) AF: 0.00 AC: 0 AN: 56690

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000833 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	8.7
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.040	N
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.55	T
MutationAssessor	Pathogenic	3.9	H
PhyloP100		-3.4
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.33
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.99	D
Vest4		0.53
MutPred		0.79		Gain of disorder (P = 0.052)
MVP		0.48
MPC		0.88
ClinPred		0.99	D
GERP RS		-7.8
Varity_R		0.61
gMVP		0.65
Mutation Taster		=69/31	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs770398185; hg19: chr5-176072392;