7-2355064-C-G

Variant names:

• chr7-2355064-C-G
• NM_001037283.2:c.143C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001037283.2(EIF3B):​c.143C>G​(p.Thr48Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000183 in 1,093,238 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: EIF3B NM_001037283.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0860

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06279603).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF3B	NM_001037283.2	c.143C>G	p.Thr48Ser	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.143C>G	p.Thr48Ser	missense_variant	Exon 1 of 19	1	NM_001037283.2	ENSP00000354125.4
EIF3B	ENST00000397011.2	c.143C>G	p.Thr48Ser	missense_variant	Exon 1 of 19	1		ENSP00000380206.2
EIF3B	ENST00000413917.5	c.143C>G	p.Thr48Ser	missense_variant	Exon 1 of 7	2		ENSP00000407785.1
EIF3B	ENST00000431643.5	c.-504-170C>G		intron_variant	Intron 1 of 7	5		ENSP00000408062.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000183 AC: 2 AN: 1093238 Hom.: 0 Cov.: 29 AF XY: 0.00000384 AC XY: 2 AN XY: 520806

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000722

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 23, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.143C>G (p.T48S) alteration is located in exon 1 (coding exon 1) of the EIF3B gene. This alteration results from a C to G substitution at nucleotide position 143, causing the threonine (T) at amino acid position 48 to be replaced by a serine (S). 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	0.073
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	5.9
DANN	Benign	0.38
DEOGEN2	Benign	0.018	T;.;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0037	N
LIST_S2	Benign	0.26	.;T;T
M_CAP	Benign	0.078	D
MetaRNN	Benign	0.063	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.20	N;.;N
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.18	N;N;N
REVEL	Benign	0.018
Sift	Benign	0.36	T;T;T
Sift4G	Benign	0.79	T;T;T
Polyphen		0.0	B;.;B
Vest4		0.026
MutPred		0.14		Gain of relative solvent accessibility (P = 0.0166);Gain of relative solvent accessibility (P = 0.0166);Gain of relative solvent accessibility (P = 0.0166);
MVP		0.21
MPC		0.34
ClinPred		0.055	T
GERP RS		-0.027
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.1
Varity_R		0.033
gMVP		0.081

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: chr7-2394699;