7-2355064-C-T

Variant names:

• chr7-2355064-C-T
• rs1779318006
• NM_001037283.2:c.143C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001037283.2(EIF3B):​c.143C>T​(p.Thr48Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000915 in 1,093,238 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T48S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 9.1e-7 (0 hom.)
• Consequence: EIF3B NM_001037283.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10407311).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001037283.2. 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
	EIF3B	NM_001037283.2	MANE Select	c.143C>T	p.Thr48Ile	missense	Exon 1 of 19	NP_001032360.1	P55884-1
	EIF3B	NM_001362791.2		c.143C>T	p.Thr48Ile	missense	Exon 1 of 19	NP_001349720.1	P55884-1
	EIF3B	NM_003751.4		c.143C>T	p.Thr48Ile	missense	Exon 1 of 19	NP_003742.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF3B	ENST00000360876.9	TSL:1 MANE Select	c.143C>T	p.Thr48Ile	missense	Exon 1 of 19	ENSP00000354125.4	P55884-1
	EIF3B	ENST00000397011.2	TSL:1	c.143C>T	p.Thr48Ile	missense	Exon 1 of 19	ENSP00000380206.2	P55884-1
	EIF3B	ENST00000899983.1		c.143C>T	p.Thr48Ile	missense	Exon 1 of 19	ENSP00000570042.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.15e-7 AC: 1 AN: 1093238 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 520806

African (AFR) AF: 0.00 AC: 0 AN: 22510

American (AMR) AF: 0.00 AC: 0 AN: 8038

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14094

East Asian (EAS) AF: 0.00 AC: 0 AN: 25484

South Asian (SAS) AF: 0.00 AC: 0 AN: 27702

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22150

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2918

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 926810

Other (OTH) AF: 0.0000230 AC: 1 AN: 43532

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	12
DANN	Benign	0.90
DEOGEN2	Benign	0.018	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.42	T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.086
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.33	N
REVEL	Benign	0.0060
Sift	Uncertain	0.012	D
Sift4G	Benign	0.15	T
Polyphen		0.037	B
Vest4		0.055
MutPred		0.24		Gain of sheet (P = 0.0125)
MVP		0.28
MPC		0.40
ClinPred		0.063	T
GERP RS		-0.027
PromoterAI		0.030	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.1
Varity_R		0.035
gMVP		0.13
Mutation Taster		=100/0	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: rs1779318006; hg19: chr7-2394699;