5-140548919-C-G

Position:

• chr5-140548919-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP6

The NM_003732.3(EIF4EBP3):​c.117C>G​(p.Ile39Met) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EIF4EBP3 NM_003732.3 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 4.27

Genes affected

EIF4EBP3 (HGNC:3290): (eukaryotic translation initiation factor 4E binding protein 3) This gene encodes a member of the EIF4EBP family, which consists of proteins that bind to eukaryotic translation initiation factor 4E and regulate its assembly into EIF4F, the multi-subunit translation initiation factor that recognizes the mRNA cap structure. Read-through transcription from the neighboring upstream gene (MASK or ANKHD1) generates a transcript (MASK-BP3) that encodes a protein comprised of the MASK protein sequence for the majority of the protein and a different C-terminus due to an alternate reading frame for the EIF4EBP3 segments. [provided by RefSeq, Oct 2010]

ANKHD1-EIF4EBP3 (HGNC:33530): (ANKHD1-EIF4EBP3 readthrough) The ANKHD1-EIF4EBP3 mRNA is an infrequent but naturally occurring readthrough transcript of the neighboring ANKHD1 and EIF4EBP3 genes. This readthrough transcript encodes a protein composed mostly of the multiple ankyrin repeats, single KH-domain protein, with its C-terminus encoded in a different reading frame from the shared portion of the EIF4EBP3 gene. The significance of this readthrough mRNA and the function of its protein product have not yet been determined. [provided by RefSeq, Nov 2009]

SRA1 (HGNC:11281): (steroid receptor RNA activator 1) Both long non-coding and protein-coding RNAs are transcribed from this gene, and they represent alternatively spliced transcript variants. This gene was initially defined as a non-coding RNA, which is a coactivator for several nuclear receptors (NRs) and is associated with breast cancer. It has now been found that this gene is involved in the regulation of many NR and non-NR activities, including metabolism, adipogenesis and chromatin organization. The long non-coding RNA transcripts interact with a variety of proteins, including the protein encoded by this gene. The encoded protein acts as a transcriptional repressor by binding to the non-coding RNA. [provided by RefSeq, Mar 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 5-140548919-C-G is Benign according to our data. Variant chr5-140548919-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2681256.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF4EBP3	NM_003732.3	c.117C>G	p.Ile39Met	missense_variant	2/3	ENST00000310331.3	NP_003723.1
ANKHD1-EIF4EBP3	NM_020690.6	c.7693C>G	p.Leu2565Val	missense_variant	35/36		NP_065741.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF4EBP3	ENST00000310331.3	c.117C>G	p.Ile39Met	missense_variant	2/3	1	NM_003732.3	ENSP00000308472.2
ANKHD1-EIF4EBP3	ENST00000532219.5	c.7693C>G	p.Leu2565Val	missense_variant	35/36	2		ENSP00000432016.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

EBV-positive nodal T- and NK-cell lymphoma Benign:1

Likely benign, no assertion criteria provided

research

Department of Clinical Pathology, School of Medicine, Fujita Health University

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.51	D
Eigen	Benign	0.11
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-0.48	T
MutationAssessor	Pathogenic	3.3	M
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.62
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.021	B
Vest4		0.52
MutPred		0.75		Loss of catalytic residue at I39 (P = 0.0726);
MVP		0.20
MPC		0.21
ClinPred		0.97	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.57
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-139928504;