chr5-176633845-G-A

Position:

• chr5-176633845-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001099408.2(EIF4E1B):​c.-202+2781G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 151,980 control chromosomes in the GnomAD database, including 12,559 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 0.38 (12559 hom., cov: 31)
• Consequence: EIF4E1B NM_001099408.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF4E1B	NM_001099408.2	c.-202+2781G>A		intron_variant		ENST00000318682.11	NP_001092878.1
EIF4E1B	NM_001375362.1	c.-214+2781G>A		intron_variant			NP_001362291.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF4E1B	ENST00000318682.11	c.-202+2781G>A		intron_variant		5	NM_001099408.2	ENSP00000323714	P1

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57907 AN: 151862 Hom.: 12550 Cov.: 31

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.0162

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.389

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

GnomAD4 genome AF: 0.381 AC: 57929 AN: 151980 Hom.: 12559 Cov.: 31 AF XY: 0.374 AC XY: 27765 AN XY: 74254

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.447

Gnomad4 ASJ AF: 0.411

Gnomad4 EAS AF: 0.0162

Gnomad4 SAS AF: 0.243

Gnomad4 FIN AF: 0.463

Gnomad4 NFE AF: 0.485

Gnomad4 OTH AF: 0.385

Alfa AF: 0.458 Hom.: 33225

Bravo AF: 0.374

Asia WGS AF: 0.135 AC: 472 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.4
DANN	Benign	0.80

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: rs1352303; hg19: chr5-176060846;