rs266719

Positions:

• chr3-186783859-T-C
• chr3-186783859-T-G

Variant summary

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

The NM_001967.4(EIF4A2):​c.29+220T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.807 in 648,812 control chromosomes in the GnomAD database, including 212,250 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 0.83 (53276 hom., cov: 32)
  • Exomes 𝑓: 0.80 (158974 hom.)
• Consequence: EIF4A2 NM_001967.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

Genes affected

EIF4A2 (HGNC:3284): (eukaryotic translation initiation factor 4A2) Enables ATP hydrolysis activity. Involved in negative regulation of RNA-directed 5'-3' RNA polymerase activity. Located in perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF4A2	NM_001967.4	c.29+220T>C		intron_variant		ENST00000323963.10	NP_001958.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF4A2	ENST00000323963.10	c.29+220T>C		intron_variant		1	NM_001967.4	ENSP00000326381	P4
	ENST00000577781.1	n.321A>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.834 AC: 126799 AN: 152064 Hom.: 53215 Cov.: 32

Gnomad AFR AF: 0.926

Gnomad AMI AF: 0.802

Gnomad AMR AF: 0.833

Gnomad ASJ AF: 0.765

Gnomad EAS AF: 0.903

Gnomad SAS AF: 0.784

Gnomad FIN AF: 0.841

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.779

Gnomad OTH AF: 0.820

GnomAD4 exome AF: 0.799 AC: 396741 AN: 496630 Hom.: 158974 Cov.: 6 AF XY: 0.798 AC XY: 206924 AN XY: 259464

Gnomad4 AFR exome AF: 0.927

Gnomad4 AMR exome AF: 0.820

Gnomad4 ASJ exome AF: 0.760

Gnomad4 EAS exome AF: 0.924

Gnomad4 SAS exome AF: 0.769

Gnomad4 FIN exome AF: 0.839

Gnomad4 NFE exome AF: 0.781

Gnomad4 OTH exome AF: 0.805

GnomAD4 genome AF: 0.834 AC: 126919 AN: 152182 Hom.: 53276 Cov.: 32 AF XY: 0.835 AC XY: 62120 AN XY: 74398

Gnomad4 AFR AF: 0.926

Gnomad4 AMR AF: 0.834

Gnomad4 ASJ AF: 0.765

Gnomad4 EAS AF: 0.902

Gnomad4 SAS AF: 0.784

Gnomad4 FIN AF: 0.841

Gnomad4 NFE AF: 0.779

Gnomad4 OTH AF: 0.822

Alfa AF: 0.790 Hom.: 65508

Bravo AF: 0.835

Asia WGS AF: 0.869 AC: 3020 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	2.4
DANN	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs266719; hg19: chr3-186501648;