NM_004096.5:c.95A>C

Variant names:

• chr10-70404496-A-C
• rs1844947142
• NM_004096.5:c.95A>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004096.5(EIF4EBP2):​c.95A>C​(p.His32Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000658 in 152,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000097 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EIF4EBP2 NM_004096.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.90
• Publications: 0 publications found

Genes affected

EIF4EBP2 (HGNC:3289): (eukaryotic translation initiation factor 4E binding protein 2) This gene encodes a member of the eukaryotic translation initiation factor 4E binding protein family. The gene products of this family bind eIF4E and inhibit translation initiation. However, insulin and other growth factors can release this inhibition via a phosphorylation-dependent disruption of their binding to eIF4E. Regulation of protein production through these gene products have been implicated in cell proliferation, cell differentiation and viral infection. [provided by RefSeq, Oct 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37711504).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004096.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF4EBP2	NM_004096.5	MANE Select	c.95A>C	p.His32Pro	missense	Exon 1 of 3	NP_004087.1	Q13542

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF4EBP2	ENST00000373218.5	TSL:1 MANE Select	c.95A>C	p.His32Pro	missense	Exon 1 of 3	ENSP00000362314.4	Q13542
	EIF4EBP2	ENST00000892260.1		c.95A>C	p.His32Pro	missense	Exon 1 of 2	ENSP00000562319.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151924 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000967 AC: 14 AN: 1447046 Hom.: 0 Cov.: 32 AF XY: 0.00000833 AC XY: 6 AN XY: 719974

African (AFR) AF: 0.00 AC: 0 AN: 31066

American (AMR) AF: 0.00 AC: 0 AN: 44080

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25664

East Asian (EAS) AF: 0.000342 AC: 13 AN: 38054

South Asian (SAS) AF: 0.00 AC: 0 AN: 85136

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51890

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4386

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1107084

Other (OTH) AF: 0.00 AC: 0 AN: 59686

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152032 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74332

African (AFR) AF: 0.00 AC: 0 AN: 41486

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67900

Other (OTH) AF: 0.00 AC: 0 AN: 2106

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.016	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	22
DANN	Benign	0.93
DEOGEN2	Benign	0.30	T
Eigen	Benign	-0.098
Eigen_PC	Benign	-0.040
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.71	T
M_CAP	Pathogenic	0.40	D
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.8	L
PhyloP100		3.9
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.95	N
REVEL	Benign	0.20
Sift	Benign	0.24	T
Sift4G	Benign	0.32	T
Polyphen		0.27	B
Vest4		0.39
MutPred		0.39		Gain of catalytic residue at P31 (P = 0.0126)
MVP		0.42
MPC		0.83
ClinPred		0.71	D
GERP RS		2.6
PromoterAI		-0.16	Neutral
Varity_R		0.16
gMVP		0.77
Mutation Taster		=53/47	polymorphism

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: rs1844947142; hg19: chr10-72164252;