NM_001037283.2:c.97G>C

Variant names:

• chr7-2355018-G-C
• rs1239400546
• NM_001037283.2:c.97G>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001037283.2(EIF3B):​c.97G>C​(p.Gly33Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000203 in 1,183,668 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G33A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: EIF3B NM_001037283.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.436
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10559532).
• BS2: High AC in GnomAdExome4 at 22 AD gene.

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.97G>C	p.Gly33Arg	missense	Exon 1 of 19	NP_001032360.1	P55884-1
	EIF3B	NM_001362791.2		c.97G>C	p.Gly33Arg	missense	Exon 1 of 19	NP_001349720.1	P55884-1
	EIF3B	NM_003751.4		c.97G>C	p.Gly33Arg	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.97G>C	p.Gly33Arg	missense	Exon 1 of 19	ENSP00000354125.4	P55884-1
	EIF3B	ENST00000397011.2	TSL:1	c.97G>C	p.Gly33Arg	missense	Exon 1 of 19	ENSP00000380206.2	P55884-1
	EIF3B	ENST00000899983.1		c.97G>C	p.Gly33Arg	missense	Exon 1 of 19	ENSP00000570042.1

Frequencies

GnomAD3 genomes AF: 0.0000134 AC: 2 AN: 149674 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000298

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000213 AC: 22 AN: 1033994 Hom.: 0 Cov.: 29 AF XY: 0.0000204 AC XY: 10 AN XY: 489058

African (AFR) AF: 0.00 AC: 0 AN: 21092

American (AMR) AF: 0.00 AC: 0 AN: 6698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11918

East Asian (EAS) AF: 0.00 AC: 0 AN: 21606

South Asian (SAS) AF: 0.00 AC: 0 AN: 19470

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 19200

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2650

European-Non Finnish (NFE) AF: 0.0000236 AC: 21 AN: 891498

Other (OTH) AF: 0.0000251 AC: 1 AN: 39862

GnomAD4 genome AF: 0.0000134 AC: 2 AN: 149674 Hom.: 0 Cov.: 32 AF XY: 0.0000137 AC XY: 1 AN XY: 73008

African (AFR) AF: 0.00 AC: 0 AN: 41150

American (AMR) AF: 0.00 AC: 0 AN: 15050

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3442

East Asian (EAS) AF: 0.00 AC: 0 AN: 5126

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9640

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.0000298 AC: 2 AN: 67160

Other (OTH) AF: 0.00 AC: 0 AN: 2056

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	0.18
BayesDel_addAF	Benign	-0.093	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	17
DANN	Benign	0.53
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.082	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.44
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.072
Sift	Benign	0.15	T
Sift4G	Benign	0.077	T
Polyphen		0.037	B
Vest4		0.037
MutPred		0.21		Loss of loop (P = 0.0112)
MVP		0.31
MPC		0.45
ClinPred		0.18	T
GERP RS		3.2
PromoterAI		0.049	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.099
gMVP		0.21
Mutation Taster		=97/3	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: rs1239400546; hg19: chr7-2394653;