NM_001417.7:c.*98C>G

Variant names:

• chr12-53040321-C-G
• rs4825
• NM_001417.7:c.*98C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001417.7(EIF4B):​c.*98C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 9.3e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EIF4B NM_001417.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.731
• Publications: 19 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.22).

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.*98C>G		3_prime_UTR	Exon 15 of 15	NP_001408.2	P23588-1
	EIF4B	NM_001300821.3		c.*98C>G		3_prime_UTR	Exon 15 of 15	NP_001287750.1	E7EX17
	EIF4B	NM_001330654.2		c.*98C>G		3_prime_UTR	Exon 14 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.*98C>G		3_prime_UTR	Exon 15 of 15	ENSP00000262056.9	P23588-1
	EIF4B	ENST00000961691.1		c.*98C>G		3_prime_UTR	Exon 15 of 15	ENSP00000631750.1
	EIF4B	ENST00000961687.1		c.*98C>G		3_prime_UTR	Exon 15 of 15	ENSP00000631746.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 9.31e-7 AC: 1 AN: 1074688 Hom.: 0 Cov.: 13 AF XY: 0.00 AC XY: 0 AN XY: 541460

African (AFR) AF: 0.00 AC: 0 AN: 24416

American (AMR) AF: 0.00 AC: 0 AN: 29770

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20538

East Asian (EAS) AF: 0.00 AC: 0 AN: 36118

South Asian (SAS) AF: 0.00 AC: 0 AN: 66664

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48566

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3200

European-Non Finnish (NFE) AF: 0.00000125 AC: 1 AN: 799144

Other (OTH) AF: 0.00 AC: 0 AN: 46272

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 6218

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
CADD	Benign	17
DANN	Benign	0.87
PhyloP100		0.73

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: rs4825; hg19: chr12-53434105;