rs4825

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr12-53040321-C-A
• chr12-53040321-C-G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001417.7(EIF4B):​c.*98C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 152,120 control chromosomes in the GnomAD database, including 34,320 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 0.60 (34320 hom., cov: 32)
  • Exomes 𝑓: 0.78 (343068 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.2).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

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

Frequencies

GnomAD3 genomes AF: 0.604 AC: 91762 AN: 152004 Hom.: 34329 Cov.: 32

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.848

Gnomad AMR AF: 0.625

Gnomad ASJ AF: 0.859

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.562

Gnomad FIN AF: 0.728

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.851

Gnomad OTH AF: 0.675

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.783 AC: 840399 AN: 1072688 Hom.: 343068 Cov.: 13 AF XY: 0.781 AC XY: 421990 AN XY: 540442

African (AFR) AF: 0.145 AC: 3527 AN: 24390

American (AMR) AF: 0.568 AC: 16873 AN: 29680

Ashkenazi Jewish (ASJ) AF: 0.851 AC: 17463 AN: 20514

East Asian (EAS) AF: 0.334 AC: 12048 AN: 36048

South Asian (SAS) AF: 0.597 AC: 39664 AN: 66424

European-Finnish (FIN) AF: 0.740 AC: 35860 AN: 48488

Middle Eastern (MID) AF: 0.801 AC: 2562 AN: 3198

European-Non Finnish (NFE) AF: 0.850 AC: 678340 AN: 797762

Other (OTH) AF: 0.738 AC: 34062 AN: 46184

GnomAD4 genome AF: 0.603 AC: 91748 AN: 152120 Hom.: 34320 Cov.: 32 AF XY: 0.595 AC XY: 44249 AN XY: 74354

African (AFR) AF: 0.169 AC: 7016 AN: 41492

American (AMR) AF: 0.625 AC: 9545 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.859 AC: 2979 AN: 3468

East Asian (EAS) AF: 0.295 AC: 1528 AN: 5182

South Asian (SAS) AF: 0.565 AC: 2719 AN: 4816

European-Finnish (FIN) AF: 0.728 AC: 7709 AN: 10586

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.851 AC: 57850 AN: 67990

Other (OTH) AF: 0.667 AC: 1405 AN: 2106

Alfa AF: 0.668 Hom.: 6218

Bravo AF: 0.576

Asia WGS AF: 0.398 AC: 1387 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.20
CADD	Benign	17
DANN	Benign	0.88
PhyloP100		0.73
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV50403220; COSMIC: COSV50403220;