rs4868672

Variant names:

• chr5-176636548-C-G
• rs4868672
• NM_001099408.2:c.-202+5484C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001099408.2(EIF4E1B):​c.-202+5484C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 152,162 control chromosomes in the GnomAD database, including 5,225 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.26 (5225 hom., cov: 33)
• Consequence: EIF4E1B NM_001099408.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.329
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF4E1B	NM_001099408.2	MANE Select	c.-202+5484C>G		intron	N/A	NP_001092878.1
	EIF4E1B	NM_001375362.1		c.-214+5484C>G		intron	N/A	NP_001362291.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF4E1B	ENST00000318682.11	TSL:5 MANE Select	c.-202+5484C>G		intron	N/A	ENSP00000323714.6
	EIF4E1B	ENST00000647833.1		c.-359-778C>G		intron	N/A	ENSP00000497422.1
	EIF4E1B	ENST00000510660.5	TSL:4	c.-202+5484C>G		intron	N/A	ENSP00000421009.1

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38882 AN: 152044 Hom.: 5226 Cov.: 33

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.345

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.256 AC: 38903 AN: 152162 Hom.: 5225 Cov.: 33 AF XY: 0.257 AC XY: 19134 AN XY: 74400

African (AFR) AF: 0.187 AC: 7779 AN: 41520

American (AMR) AF: 0.217 AC: 3320 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1085 AN: 3472

East Asian (EAS) AF: 0.345 AC: 1778 AN: 5160

South Asian (SAS) AF: 0.349 AC: 1683 AN: 4824

European-Finnish (FIN) AF: 0.258 AC: 2725 AN: 10582

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.287 AC: 19516 AN: 67984

Other (OTH) AF: 0.275 AC: 581 AN: 2116

Alfa AF: 0.270 Hom.: 653

Bravo AF: 0.249

Asia WGS AF: 0.326 AC: 1137 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.7
DANN	Benign	0.79
PhyloP100		0.33
Mutation Taster		=100/0	polymorphism (auto)

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: rs4868672; hg19: chr5-176063549;