NM_001099408.2:c.-202+2781G>A

Variant names:

• chr5-176633845-G-A
• rs1352303
• NM_001099408.2:c.-202+2781G>A

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+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
• Publications: 8 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=-0.89).
• 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 rank	MANE	Protein	UniProt
EIF4E1B	NM_001099408.2	c.-202+2781G>A		intron_variant	Intron 1 of 8	ENST00000318682.11	NP_001092878.1
EIF4E1B	NM_001375362.1	c.-214+2781G>A		intron_variant	Intron 1 of 8		NP_001362291.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF4E1B	ENST00000318682.11	c.-202+2781G>A		intron_variant	Intron 1 of 8	5	NM_001099408.2	ENSP00000323714.6

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

African (AFR) AF: 0.222 AC: 9181 AN: 41442

American (AMR) AF: 0.447 AC: 6815 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1427 AN: 3470

East Asian (EAS) AF: 0.0162 AC: 84 AN: 5182

South Asian (SAS) AF: 0.243 AC: 1171 AN: 4828

European-Finnish (FIN) AF: 0.463 AC: 4888 AN: 10550

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.485 AC: 32969 AN: 67946

Other (OTH) AF: 0.385 AC: 812 AN: 2110

Alfa AF: 0.448 Hom.: 67489

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
PhyloP100		-0.0010
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: rs1352303; hg19: chr5-176060846;