chr12-53039282-G-A

Position:

• chr12-53039282-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001417.7(EIF4B):​c.1621G>A​(p.Gly541Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EIF4B NM_001417.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.13

Genes affected

EIF4B (HGNC:3285): (eukaryotic translation initiation factor 4B) Enables RNA binding activity. Predicted to be involved in eukaryotic translation initiation factor 4F complex assembly and formation of translation preinitiation complex. Located in cytosol. Biomarker of autism spectrum disorder and major depressive disorder. [provided by Alliance of Genome Resources, Apr 2022]

TNS2-AS1 (HGNC:27464): (TNS2 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF4B	NM_001417.7	c.1621G>A	p.Gly541Arg	missense_variant	13/15	ENST00000262056.14	NP_001408.2
EIF4B	NM_001300821.3	c.1636G>A	p.Gly546Arg	missense_variant	13/15		NP_001287750.1
EIF4B	NM_001330654.2	c.1504G>A	p.Gly502Arg	missense_variant	12/14		NP_001317583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF4B	ENST00000262056.14	c.1621G>A	p.Gly541Arg	missense_variant	13/15	1	NM_001417.7	ENSP00000262056	P4
TNS2-AS1	ENST00000552905.6	n.320+6679C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 29, 2022

The c.1621G>A (p.G541R) alteration is located in exon 13 (coding exon 13) of the EIF4B gene. This alteration results from a G to A substitution at nucleotide position 1621, causing the glycine (G) at amino acid position 541 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.14	T;.;.
Eigen	Pathogenic	0.70
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.87	D;D;D
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.66	D;D;D
MetaSVM	Benign	-0.30	T
MutationAssessor	Uncertain	2.4	M;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.3	N;N;N
REVEL	Benign	0.23
Sift	Uncertain	0.0090	D;D;D
Sift4G	Benign	0.17	T;T;T
Polyphen		1.0	D;D;.
Vest4		0.63
MutPred		0.41		.;Gain of catalytic residue at R550 (P = 0.0014);.;
MVP		0.73
MPC		0.26
ClinPred		0.94	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.18
gMVP		0.092

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-53433066;