10-119073292-C-T

Position:

• chr10-119073292-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.377+149G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 697,696 control chromosomes in the GnomAD database, including 109,591 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 0.51 (20809 hom., cov: 33)
  • Exomes 𝑓: 0.57 (88782 hom.)
• Consequence: EIF3A NM_003750.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.275

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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF3A	NM_003750.4	c.377+149G>A		intron_variant		ENST00000369144.8	NP_003741.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF3A	ENST00000369144.8	c.377+149G>A		intron_variant		1	NM_003750.4	ENSP00000358140.3

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76904 AN: 151894 Hom.: 20803 Cov.: 33

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.719

Gnomad AMR AF: 0.598

Gnomad ASJ AF: 0.655

Gnomad EAS AF: 0.491

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.568

GnomAD4 exome AF: 0.566 AC: 309123 AN: 545684 Hom.: 88782 AF XY: 0.570 AC XY: 161018 AN XY: 282476

Gnomad4 AFR exome AF: 0.307

Gnomad4 AMR exome AF: 0.591

Gnomad4 ASJ exome AF: 0.660

Gnomad4 EAS exome AF: 0.536

Gnomad4 SAS exome AF: 0.646

Gnomad4 FIN exome AF: 0.599

Gnomad4 NFE exome AF: 0.562

Gnomad4 OTH exome AF: 0.566

GnomAD4 genome AF: 0.506 AC: 76926 AN: 152012 Hom.: 20809 Cov.: 33 AF XY: 0.513 AC XY: 38102 AN XY: 74282

Gnomad4 AFR AF: 0.306

Gnomad4 AMR AF: 0.599

Gnomad4 ASJ AF: 0.655

Gnomad4 EAS AF: 0.491

Gnomad4 SAS AF: 0.647

Gnomad4 FIN AF: 0.612

Gnomad4 NFE AF: 0.569

Gnomad4 OTH AF: 0.568

Alfa AF: 0.530 Hom.: 2758

Bravo AF: 0.494

Asia WGS AF: 0.570 AC: 1979 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.4
DANN	Benign	0.27

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: rs1397617; hg19: chr10-120832804; COSMIC: COSV64960946;