rs4868672

Positions:

• chr5-176636548-C-G

Variant summary

Our verdict is Benign. Variant got -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

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]

EIF4E1B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF4E1B	NM_001099408.2	c.-202+5484C>G		intron_variant		ENST00000318682.11	NP_001092878.1
EIF4E1B	NM_001375362.1	c.-214+5484C>G		intron_variant			NP_001362291.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF4E1B	ENST00000318682.11	c.-202+5484C>G		intron_variant		5	NM_001099408.2	ENSP00000323714.6

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

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.313

Gnomad4 EAS AF: 0.345

Gnomad4 SAS AF: 0.349

Gnomad4 FIN AF: 0.258

Gnomad4 NFE AF: 0.287

Gnomad4 OTH AF: 0.275

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.7
DANN	Benign	0.79

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

Publications

LitVar

Other links and lift over

dbSNP: rs4868672; hg19: chr5-176063549;