rs9325559

chr10-119062113-C-T

Variant summary

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

The NM_003750.4(EIF3A):c.1123-785G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,084 control chromosomes in the GnomAD database, including 2,002 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 0.16 (2002 hom., cov: 31)
• Consequence: EIF3A NM_003750.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.746

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EIF3A	NM_003750.4	c.1123-785G>A		intron_variant		ENST00000369144.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EIF3A	ENST00000369144.8	c.1123-785G>A		intron_variant		1	NM_003750.4	P1

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23628 AN: 151966 Hom.: 2000 Cov.: 31

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.00423

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.134

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.155 AC: 23638 AN: 152084 Hom.: 2002 Cov.: 31 AF XY: 0.154 AC XY: 11442 AN XY: 74350

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.182

Gnomad4 ASJ AF: 0.134

Gnomad4 EAS AF: 0.00424

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.179

Gnomad4 OTH AF: 0.132

Alfa AF: 0.169 Hom.: 3021

Bravo AF: 0.155

Asia WGS AF: 0.0750 AC: 262 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.56
Dann	Benign	0.13

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: rs9325559; hg19: chr10-120821625;