chr7-2355001-A-C

Variant names:

• chr7-2355001-A-C
• NM_001037283.2:c.80A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001037283.2(EIF3B):​c.80A>C​(p.Glu27Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EIF3B NM_001037283.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0420

Genes affected

EIF3B (HGNC:3280): (eukaryotic translation initiation factor 3 subunit B) Enables RNA binding activity. Contributes to translation initiation factor activity. Involved in several processes, including IRES-dependent viral translational initiation; translational initiation; and viral translational termination-reinitiation. Located in extracellular exosome. Part of eukaryotic translation initiation factor 3 complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10758203).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF3B	NM_001037283.2	c.80A>C	p.Glu27Ala	missense_variant	Exon 1 of 19	ENST00000360876.9	NP_001032360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF3B	ENST00000360876.9	c.80A>C	p.Glu27Ala	missense_variant	Exon 1 of 19	1	NM_001037283.2	ENSP00000354125.4
EIF3B	ENST00000397011.2	c.80A>C	p.Glu27Ala	missense_variant	Exon 1 of 19	1		ENSP00000380206.2
EIF3B	ENST00000413917.5	c.80A>C	p.Glu27Ala	missense_variant	Exon 1 of 7	2		ENSP00000407785.1
EIF3B	ENST00000431643.5	c.-504-233A>C		intron_variant	Intron 1 of 7	5		ENSP00000408062.1

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

Jun 22, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.80A>C (p.E27A) alteration is located in exon 1 (coding exon 1) of the EIF3B gene. This alteration results from a A to C substitution at nucleotide position 80, causing the glutamic acid (E) at amino acid position 27 to be replaced by an alanine (A). 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	0.069
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	22
DANN	Benign	0.90
DEOGEN2	Benign	0.019	T;.;T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.50	.;T;T
M_CAP	Benign	0.072	D
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N;.;N
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.30	N;N;N
REVEL	Benign	0.043
Sift	Uncertain	0.0060	D;D;D
Sift4G	Uncertain	0.019	D;T;D
Polyphen		0.0	B;.;B
Vest4		0.18
MutPred		0.21		Loss of solvent accessibility (P = 0.0111);Loss of solvent accessibility (P = 0.0111);Loss of solvent accessibility (P = 0.0111);
MVP		0.38
MPC		0.40
ClinPred		0.16	T
GERP RS		1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.12
gMVP		0.18

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: chr7-2394636;