rs952253

Variant names:

• chr10-119069792-G-A
• rs952253
• NM_003750.4:c.742-138C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
EIF3A	NM_003750.4	c.742-138C>T		intron_variant	Intron 5 of 21	ENST00000369144.8	NP_003741.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF3A	ENST00000369144.8	c.742-138C>T		intron_variant	Intron 5 of 21	1	NM_003750.4	ENSP00000358140.3

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

African (AFR) AF: 0.190 AC: 2376 AN: 12498

American (AMR) AF: 0.0320 AC: 585 AN: 18300

Ashkenazi Jewish (ASJ) AF: 0.0123 AC: 169 AN: 13750

East Asian (EAS) AF: 0.0600 AC: 1873 AN: 31196

South Asian (SAS) AF: 0.00984 AC: 440 AN: 44702

European-Finnish (FIN) AF: 0.0124 AC: 371 AN: 29832

Middle Eastern (MID) AF: 0.0292 AC: 58 AN: 1986

European-Non Finnish (NFE) AF: 0.0266 AC: 7361 AN: 276948

Other (OTH) AF: 0.0376 AC: 987 AN: 26276

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

African (AFR) AF: 0.191 AC: 7940 AN: 41486

American (AMR) AF: 0.0413 AC: 631 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0110 AC: 38 AN: 3470

East Asian (EAS) AF: 0.0517 AC: 268 AN: 5186

South Asian (SAS) AF: 0.0104 AC: 50 AN: 4830

European-Finnish (FIN) AF: 0.0109 AC: 115 AN: 10594

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0281 AC: 1910 AN: 68014

Other (OTH) AF: 0.0629 AC: 133 AN: 2116

Alfa AF: 0.0431 Hom.: 103

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
PhyloP100		-0.37
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs952253; hg19: chr10-120829304;