8-38044935-C-T

Variant names:

• chr8-38044935-C-T
• rs6605631
• NM_004095.4:c.146-12146C>T

Variant summary

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

The NM_004095.4(EIF4EBP1):​c.146-12146C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 151,942 control chromosomes in the GnomAD database, including 40,325 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 0.72 (40325 hom., cov: 30)
• Consequence: EIF4EBP1 NM_004095.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.497
• Publications: 4 publications found

Genes affected

EIF4EBP1 (HGNC:3288): (eukaryotic translation initiation factor 4E binding protein 1) This gene encodes one member of a family of translation repressor proteins. The protein directly interacts with eukaryotic translation initiation factor 4E (eIF4E), which is a limiting component of the multisubunit complex that recruits 40S ribosomal subunits to the 5' end of mRNAs. Interaction of this protein with eIF4E inhibits complex assembly and represses translation. This protein is phosphorylated in response to various signals including UV irradiation and insulin signaling, resulting in its dissociation from eIF4E and activation of mRNA translation. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF4EBP1	NM_004095.4	c.146-12146C>T		intron_variant	Intron 1 of 2	ENST00000338825.5	NP_004086.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF4EBP1	ENST00000338825.5	c.146-12146C>T		intron_variant	Intron 1 of 2	1	NM_004095.4	ENSP00000340691.4

Frequencies

GnomAD3 genomes AF: 0.724 AC: 109942 AN: 151824 Hom.: 40322 Cov.: 30

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.932

Gnomad AMR AF: 0.748

Gnomad ASJ AF: 0.827

Gnomad EAS AF: 0.594

Gnomad SAS AF: 0.678

Gnomad FIN AF: 0.757

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.784

Gnomad OTH AF: 0.758

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

GnomAD4 genome AF: 0.724 AC: 109971 AN: 151942 Hom.: 40325 Cov.: 30 AF XY: 0.722 AC XY: 53640 AN XY: 74260

African (AFR) AF: 0.613 AC: 25398 AN: 41412

American (AMR) AF: 0.748 AC: 11391 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.827 AC: 2867 AN: 3468

East Asian (EAS) AF: 0.593 AC: 3051 AN: 5142

South Asian (SAS) AF: 0.679 AC: 3275 AN: 4826

European-Finnish (FIN) AF: 0.757 AC: 7990 AN: 10558

Middle Eastern (MID) AF: 0.871 AC: 256 AN: 294

European-Non Finnish (NFE) AF: 0.784 AC: 53298 AN: 67994

Other (OTH) AF: 0.760 AC: 1595 AN: 2100

Alfa AF: 0.774 Hom.: 60985

Bravo AF: 0.720

Asia WGS AF: 0.634 AC: 2204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.58
DANN	Benign	0.54
PhyloP100		-0.50
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: rs6605631; hg19: chr8-37902453;