7-2355039-C-T

Variant names:

• chr7-2355039-C-T
• rs955950785
• NM_001037283.2:c.118C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001037283.2(EIF3B):​c.118C>T​(p.Pro40Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000283 in 1,203,484 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. P40T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000029 (0 hom.)
• Consequence: EIF3B NM_001037283.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.704
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.05477941).
• BS2: High AC in GnomAdExome4 at 31 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.118C>T	p.Pro40Ser	missense	Exon 1 of 19	NP_001032360.1	P55884-1
	EIF3B	NM_001362791.2		c.118C>T	p.Pro40Ser	missense	Exon 1 of 19	NP_001349720.1	P55884-1
	EIF3B	NM_003751.4		c.118C>T	p.Pro40Ser	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.118C>T	p.Pro40Ser	missense	Exon 1 of 19	ENSP00000354125.4	P55884-1
	EIF3B	ENST00000397011.2	TSL:1	c.118C>T	p.Pro40Ser	missense	Exon 1 of 19	ENSP00000380206.2	P55884-1
	EIF3B	ENST00000899983.1		c.118C>T	p.Pro40Ser	missense	Exon 1 of 19	ENSP00000570042.1

Frequencies

GnomAD3 genomes AF: 0.0000200 AC: 3 AN: 149816 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: 0.0000446

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000294 AC: 31 AN: 1053668 Hom.: 0 Cov.: 29 AF XY: 0.0000341 AC XY: 17 AN XY: 498288

African (AFR) AF: 0.00 AC: 0 AN: 21782

American (AMR) AF: 0.00 AC: 0 AN: 7378

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12896

East Asian (EAS) AF: 0.00 AC: 0 AN: 23718

South Asian (SAS) AF: 0.00 AC: 0 AN: 19828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2778

European-Non Finnish (NFE) AF: 0.0000343 AC: 31 AN: 903472

Other (OTH) AF: 0.00 AC: 0 AN: 41412

GnomAD4 genome AF: 0.0000200 AC: 3 AN: 149816 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 73120

African (AFR) AF: 0.00 AC: 0 AN: 41086

American (AMR) AF: 0.00 AC: 0 AN: 15072

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3434

East Asian (EAS) AF: 0.00 AC: 0 AN: 5118

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9806

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000446 AC: 3 AN: 67210

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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

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	0.075
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	14
DANN	Benign	0.83
DEOGEN2	Benign	0.019	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.46	N
PhyloP100		-0.70
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.38	N
REVEL	Benign	0.016
Sift	Benign	0.37	T
Sift4G	Benign	0.17	T
Polyphen		0.0	B
Vest4		0.036
MutPred		0.34		Loss of relative solvent accessibility (P = 0.0071)
MVP		0.18
MPC		0.38
ClinPred		0.023	T
GERP RS		1.8
PromoterAI		-0.14	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.8
Varity_R		0.021
gMVP		0.16
Mutation Taster		=94/6	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: rs955950785; hg19: chr7-2394674;