NM_001417.7:c.392G>C

Variant names:

• chr12-53019941-G-C
• rs201365536
• NM_001417.7:c.392G>C

Variant summary

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

The NM_001417.7(EIF4B):​c.392G>C​(p.Ser131Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000343 in 1,612,602 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. S131G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00029 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00035 (0 hom.)
• Consequence: EIF4B NM_001417.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.74
• Publications: 1 publications found

Genes affected

EIF4B (HGNC:3285): (eukaryotic translation initiation factor 4B) Enables RNA binding activity. Predicted to be involved in eukaryotic translation initiation factor 4F complex assembly and formation of translation preinitiation complex. Located in cytosol. Biomarker of autism spectrum disorder and major depressive disorder. [provided by Alliance of Genome Resources, Apr 2022]

TNS2-AS1 (HGNC:27464): (TNS2 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13087097).
• BS2: High AC in GnomAd4 at 44 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001417.7. 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
	EIF4B	NM_001417.7	MANE Select	c.392G>C	p.Ser131Thr	missense	Exon 4 of 15	NP_001408.2	P23588-1
	EIF4B	NM_001300821.3		c.392G>C	p.Ser131Thr	missense	Exon 4 of 15	NP_001287750.1	E7EX17
	EIF4B	NM_001330654.2		c.360+935G>C		intron	N/A	NP_001317583.1	P23588-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF4B	ENST00000262056.14	TSL:1 MANE Select	c.392G>C	p.Ser131Thr	missense	Exon 4 of 15	ENSP00000262056.9	P23588-1
	EIF4B	ENST00000961691.1		c.392G>C	p.Ser131Thr	missense	Exon 4 of 15	ENSP00000631750.1
	EIF4B	ENST00000961687.1		c.392G>C	p.Ser131Thr	missense	Exon 4 of 15	ENSP00000631746.1

Frequencies

GnomAD3 genomes AF: 0.000289 AC: 44 AN: 152160 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000456

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000266 AC: 66 AN: 248038 AF XY: 0.000282

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000588

Gnomad ASJ exome AF: 0.0000994

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.000523

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.000349 AC: 509 AN: 1460442 Hom.: 0 Cov.: 30 AF XY: 0.000352 AC XY: 256 AN XY: 726560

African (AFR) AF: 0.0000598 AC: 2 AN: 33428

American (AMR) AF: 0.0000903 AC: 4 AN: 44284

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39642

South Asian (SAS) AF: 0.00 AC: 0 AN: 85968

European-Finnish (FIN) AF: 0.000243 AC: 13 AN: 53396

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5762

European-Non Finnish (NFE) AF: 0.000425 AC: 472 AN: 1111514

Other (OTH) AF: 0.000232 AC: 14 AN: 60338

GnomAD4 genome AF: 0.000289 AC: 44 AN: 152160 Hom.: 0 Cov.: 30 AF XY: 0.000256 AC XY: 19 AN XY: 74336

African (AFR) AF: 0.000145 AC: 6 AN: 41438

American (AMR) AF: 0.000197 AC: 3 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

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

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000456 AC: 31 AN: 68032

Other (OTH) AF: 0.000478 AC: 1 AN: 2090

Alfa AF: 0.000422 Hom.: 0

Bravo AF: 0.000314

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000856 AC: 7

ExAC AF: 0.000306 AC: 37

EpiCase AF: 0.000927

EpiControl AF: 0.00107

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	0.13
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	21
DANN	Benign	0.87
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.32
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.13	T
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Benign	0.68	N
PhyloP100		3.7
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.29
Sift	Benign	0.18	T
Sift4G	Benign	0.20	T
Polyphen		0.0060	B
Vest4		0.19
MVP		0.85
MPC		0.80
ClinPred		0.040	T
GERP RS		2.7
Varity_R		0.14
gMVP		0.31
Mutation Taster		=80/20	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: rs201365536; hg19: chr12-53413725; COSMIC: COSV50402395; COSMIC: COSV50402395;