12-53018902-G-A

Variant names:

• chr12-53018902-G-A
• rs1273467898
• NM_001417.7:c.256G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001417.7(EIF4B):​c.256G>A​(p.Asp86Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000821 in 1,461,662 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000082 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EIF4B NM_001417.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.77
• 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 -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 12 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.256G>A	p.Asp86Asn	missense	Exon 3 of 15	NP_001408.2	P23588-1
	EIF4B	NM_001300821.3		c.256G>A	p.Asp86Asn	missense	Exon 3 of 15	NP_001287750.1	E7EX17
	EIF4B	NM_001330654.2		c.256G>A	p.Asp86Asn	missense	Exon 3 of 14	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.256G>A	p.Asp86Asn	missense	Exon 3 of 15	ENSP00000262056.9	P23588-1
	EIF4B	ENST00000961691.1		c.256G>A	p.Asp86Asn	missense	Exon 3 of 15	ENSP00000631750.1
	EIF4B	ENST00000961687.1		c.256G>A	p.Asp86Asn	missense	Exon 3 of 15	ENSP00000631746.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151954 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000242

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000803 AC: 2 AN: 249138 AF XY: 0.00000740

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000821 AC: 12 AN: 1461662 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 727138

African (AFR) AF: 0.0000597 AC: 2 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00000720 AC: 8 AN: 1111864

Other (OTH) AF: 0.00 AC: 0 AN: 60376

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000658 AC: 1 AN: 151954 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74196

African (AFR) AF: 0.0000242 AC: 1 AN: 41362

American (AMR) AF: 0.00 AC: 0 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10568

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68000

Other (OTH) AF: 0.00 AC: 0 AN: 2076

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	Pathogenic	0.82
BayesDel_addAF	Uncertain	0.033	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.60	D
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.79	T
M_CAP	Uncertain	0.22	D
MetaRNN	Uncertain	0.64	D
MetaSVM	Uncertain	0.75	D
MutationAssessor	Benign	1.3	L
PhyloP100		6.8
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-3.5	D
REVEL	Uncertain	0.62
Sift	Benign	0.066	T
Sift4G	Benign	0.072	T
Polyphen		0.77	P
Vest4		0.38
MutPred		0.31		Gain of catalytic residue at L90 (P = 0)
MVP		0.91
MPC		1.5
ClinPred		0.92	D
GERP RS		4.7
Varity_R		0.50
gMVP		0.64
Mutation Taster		=66/34	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: rs1273467898; hg19: chr12-53412686;