chr10-119039143-G-A

Position:

• chr10-119039143-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.3527-704C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 151,904 control chromosomes in the GnomAD database, including 20,701 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 0.50 (20701 hom., cov: 31)
• Consequence: EIF3A NM_003750.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.519

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 (SAS) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF3A	NM_003750.4	c.3527-704C>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.3527-704C>T		intron_variant		1	NM_003750.4	ENSP00000358140	P1

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76670 AN: 151784 Hom.: 20695 Cov.: 31

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.720

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.655

Gnomad EAS AF: 0.488

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.566

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

GnomAD4 genome AF: 0.505 AC: 76692 AN: 151904 Hom.: 20701 Cov.: 31 AF XY: 0.511 AC XY: 37937 AN XY: 74228

Gnomad4 AFR AF: 0.306

Gnomad4 AMR AF: 0.598

Gnomad4 ASJ AF: 0.655

Gnomad4 EAS AF: 0.488

Gnomad4 SAS AF: 0.648

Gnomad4 FIN AF: 0.598

Gnomad4 NFE AF: 0.569

Gnomad4 OTH AF: 0.567

Alfa AF: 0.554 Hom.: 14976

Bravo AF: 0.493

Asia WGS AF: 0.570 AC: 1981 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	0.14
DANN	Benign	0.65

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: rs10787899; hg19: chr10-120798655;