chr11-7987468-C-T

Variant names:

• chr11-7987468-C-T
• rs1043738
• NM_003754.3:c.116C>T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_003754.3(EIF3F):​c.116C>T​(p.Pro39Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.026 in 1,605,270 control chromosomes in the GnomAD database, including 700 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.038 (148 hom., cov: 33)
  • Exomes 𝑓: 0.025 (552 hom.)
• Consequence: EIF3F NM_003754.3 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.78

Genes affected

EIF3F (HGNC:3275): (eukaryotic translation initiation factor 3 subunit F) Enables deubiquitinase activity and identical protein binding activity. Contributes to translation initiation factor activity. Involved in IRES-dependent viral translational initiation; protein deubiquitination; and translational initiation. Located in membrane. Part of eukaryotic translation initiation factor 3 complex. Implicated in autosomal recessive non-syndromic intellectual disability. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002229333).
• BP6: Variant 11-7987468-C-T is Benign according to our data. Variant chr11-7987468-C-T is described in ClinVar as [Benign]. Clinvar id is 3056649.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF3F	NM_003754.3	c.116C>T	p.Pro39Leu	missense_variant	Exon 1 of 8	ENST00000651655.1	NP_003745.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF3F	ENST00000651655.1	c.116C>T	p.Pro39Leu	missense_variant	Exon 1 of 8		NM_003754.3	ENSP00000499218.1

Frequencies

GnomAD3 genomes AF: 0.0382 AC: 5808 AN: 152192 Hom.: 147 Cov.: 33

Gnomad AFR AF: 0.0746

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0252

Gnomad ASJ AF: 0.0204

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.0388

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0253

Gnomad OTH AF: 0.0383

GnomAD3 exomes AF: 0.0230 AC: 5353 AN: 232710 Hom.: 105 AF XY: 0.0215 AC XY: 2763 AN XY: 128382

Gnomad AFR exome AF: 0.0755

Gnomad AMR exome AF: 0.0136

Gnomad ASJ exome AF: 0.0256

Gnomad EAS exome AF: 0.0000570

Gnomad SAS exome AF: 0.00419

Gnomad FIN exome AF: 0.0388

Gnomad NFE exome AF: 0.0255

Gnomad OTH exome AF: 0.0232

GnomAD4 exome AF: 0.0247 AC: 35855 AN: 1452960 Hom.: 552 Cov.: 31 AF XY: 0.0240 AC XY: 17326 AN XY: 722892

Gnomad4 AFR exome AF: 0.0748

Gnomad4 AMR exome AF: 0.0156

Gnomad4 ASJ exome AF: 0.0243

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00444

Gnomad4 FIN exome AF: 0.0370

Gnomad4 NFE exome AF: 0.0255

Gnomad4 OTH exome AF: 0.0240

GnomAD4 genome AF: 0.0382 AC: 5817 AN: 152310 Hom.: 148 Cov.: 33 AF XY: 0.0377 AC XY: 2805 AN XY: 74478

Gnomad4 AFR AF: 0.0746

Gnomad4 AMR AF: 0.0251

Gnomad4 ASJ AF: 0.0204

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00269

Gnomad4 FIN AF: 0.0388

Gnomad4 NFE AF: 0.0253

Gnomad4 OTH AF: 0.0379

Alfa AF: 0.0284 Hom.: 20

Bravo AF: 0.0393

TwinsUK AF: 0.0232 AC: 86

ALSPAC AF: 0.0236 AC: 91

ExAC AF: 0.0227 AC: 2649

Asia WGS AF: 0.00636 AC: 22 AN: 3476

EpiCase AF: 0.0245

EpiControl AF: 0.0256

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

EIF3F-related disorder Benign:1

Oct 28, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	16
DANN	Benign	0.81
DEOGEN2	Benign	0.0077	T;T;.
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.086	N
MetaRNN	Benign	0.0022	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L;L;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.69	N;N;.
REVEL	Benign	0.040
Sift	Benign	0.51	T;T;.
Sift4G	Benign	0.16	T;T;.
Polyphen		0.21	B;B;.
Vest4		0.097
MPC		0.28
ClinPred		0.0063	T
GERP RS		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.036
gMVP		0.31

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

LitVar

Other links and lift over

dbSNP: rs1043738; hg19: chr11-8009015; COSMIC: COSV59141570; COSMIC: COSV59141570;