rs4825

chr12-53040321-C-Achr12-53040321-C-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EIF4B	NM_001417.7	c.*98C>A		3_prime_UTR_variant	15/15	ENST00000262056.14
EIF4B	NM_001300821.3	c.*98C>A		3_prime_UTR_variant	15/15
EIF4B	NM_001330654.2	c.*98C>A		3_prime_UTR_variant	14/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EIF4B	ENST00000262056.14	c.*98C>A		3_prime_UTR_variant	15/15	1	NM_001417.7	P4
TNS2-AS1	ENST00000552905.6	n.320+5640G>T		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR exome AF: 0.145

Gnomad4 AMR exome AF: 0.568

Gnomad4 ASJ exome AF: 0.851

Gnomad4 EAS exome AF: 0.334

Gnomad4 SAS exome AF: 0.597

Gnomad4 FIN exome AF: 0.740

Gnomad4 NFE exome AF: 0.850

Gnomad4 OTH exome AF: 0.738

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

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.625

Gnomad4 ASJ AF: 0.859

Gnomad4 EAS AF: 0.295

Gnomad4 SAS AF: 0.565

Gnomad4 FIN AF: 0.728

Gnomad4 NFE AF: 0.851

Gnomad4 OTH AF: 0.667

Alfa AF: 0.684 Hom.: 6202

Bravo AF: 0.576

Asia WGS AF: 0.398 AC: 1387 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.20
Cadd	Benign	17
Dann	Benign	0.88

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

Publications

LitVar

Other links and lift over

dbSNP: rs4825; hg19: chr12-53434105; COSMIC: COSV50403220; COSMIC: COSV50403220;