rs952253

Positions:

• chr10-119069792-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003750.4(EIF3A):​c.742-138C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0417 in 607,670 control chromosomes in the GnomAD database, including 1,273 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 0.073 (816 hom., cov: 33)
  • Exomes 𝑓: 0.031 (457 hom.)
• Consequence: EIF3A NM_003750.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.369

Genes affected

EIF3A (HGNC:3271): (eukaryotic translation initiation factor 3 subunit A) Enables RNA binding activity. Contributes to translation initiation factor activity. Involved in IRES-dependent viral translational initiation; formation of cytoplasmic translation initiation complex; and viral translational termination-reinitiation. Located in cytosol; nucleolus; and nucleoplasm. Part of eukaryotic translation initiation factor 3 complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF3A	NM_003750.4	c.742-138C>T		intron_variant		ENST00000369144.8	NP_003741.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF3A	ENST00000369144.8	c.742-138C>T		intron_variant		1	NM_003750.4	ENSP00000358140	P1

Frequencies

GnomAD3 genomes AF: 0.0729 AC: 11093 AN: 152064 Hom.: 814 Cov.: 33

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0413

Gnomad ASJ AF: 0.0110

Gnomad EAS AF: 0.0518

Gnomad SAS AF: 0.0103

Gnomad FIN AF: 0.0109

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0281

Gnomad OTH AF: 0.0630

GnomAD4 exome AF: 0.0312 AC: 14220 AN: 455488 Hom.: 457 AF XY: 0.0295 AC XY: 7162 AN XY: 242496

Gnomad4 AFR exome AF: 0.190

Gnomad4 AMR exome AF: 0.0320

Gnomad4 ASJ exome AF: 0.0123

Gnomad4 EAS exome AF: 0.0600

Gnomad4 SAS exome AF: 0.00984

Gnomad4 FIN exome AF: 0.0124

Gnomad4 NFE exome AF: 0.0266

Gnomad4 OTH exome AF: 0.0376

GnomAD4 genome AF: 0.0730 AC: 11111 AN: 152182 Hom.: 816 Cov.: 33 AF XY: 0.0702 AC XY: 5224 AN XY: 74414

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.0413

Gnomad4 ASJ AF: 0.0110

Gnomad4 EAS AF: 0.0517

Gnomad4 SAS AF: 0.0104

Gnomad4 FIN AF: 0.0109

Gnomad4 NFE AF: 0.0281

Gnomad4 OTH AF: 0.0629

Alfa AF: 0.0419 Hom.: 60

Bravo AF: 0.0812

Asia WGS AF: 0.0420 AC: 146 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.0
DANN	Benign	0.36

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: rs952253; hg19: chr10-120829304;