NM_003754.3:c.653+206G>T

Variant names:

• chr11-7993230-G-T
• rs12420464
• NM_003754.3:c.653+206G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003754.3(EIF3F):​c.653+206G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0443 in 152,246 control chromosomes in the GnomAD database, including 215 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.044 (215 hom., cov: 32)
• Consequence: EIF3F NM_003754.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.205
• Publications: 8 publications found

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]

EIF3F Gene-Disease associations (from GenCC):

• syndromic intellectual disability

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• intellectual developmental disorder, autosomal recessive 67

  Inheritance: AR, Unknown Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.071 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003754.3. 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
	EIF3F	NM_003754.3	MANE Select	c.653+206G>T		intron	N/A	NP_003745.1	O00303

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF3F	ENST00000651655.1	MANE Select	c.653+206G>T		intron	N/A	ENSP00000499218.1	O00303
	EIF3F	ENST00000531572.2	TSL:2	c.653+206G>T		intron	N/A	ENSP00000434286.2	H0YDT6
	EIF3F	ENST00000533626.5	TSL:2	c.653+206G>T		intron	N/A	ENSP00000431800.1	O00303

Frequencies

GnomAD3 genomes AF: 0.0443 AC: 6746 AN: 152128 Hom.: 215 Cov.: 32

Gnomad AFR AF: 0.0136

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.0313

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0250

Gnomad FIN AF: 0.0356

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0727

Gnomad OTH AF: 0.0359

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0443 AC: 6748 AN: 152246 Hom.: 215 Cov.: 32 AF XY: 0.0426 AC XY: 3171 AN XY: 74438

African (AFR) AF: 0.0136 AC: 564 AN: 41526

American (AMR) AF: 0.0312 AC: 478 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0173 AC: 60 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5176

South Asian (SAS) AF: 0.0257 AC: 124 AN: 4828

European-Finnish (FIN) AF: 0.0356 AC: 377 AN: 10600

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0727 AC: 4943 AN: 68024

Other (OTH) AF: 0.0355 AC: 75 AN: 2114

Alfa AF: 0.0588 Hom.: 575

Bravo AF: 0.0428

Asia WGS AF: 0.0100 AC: 35 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	5.8
DANN	Benign	0.83
PhyloP100		-0.20
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: rs12420464; hg19: chr11-8014777;