3-186783859-T-G

Variant names:

• chr3-186783859-T-G
• rs266719
• NM_001967.4:c.29+220T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001967.4(EIF4A2):​c.29+220T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EIF4A2 NM_001967.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• Publications: 18 publications found

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]

EIF4A2 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with hypotonia and speech delay, with or without seizures

  Inheritance: AR, AD Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, G2P

ENSG00000263826 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF4A2	NM_001967.4	c.29+220T>G		intron_variant	Intron 1 of 10	ENST00000323963.10	NP_001958.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF4A2	ENST00000323963.10	c.29+220T>G		intron_variant	Intron 1 of 10	1	NM_001967.4	ENSP00000326381.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 497278 Hom.: 0 Cov.: 6 AF XY: 0.00 AC XY: 0 AN XY: 259810

African (AFR) AF: 0.00 AC: 0 AN: 13362

American (AMR) AF: 0.00 AC: 0 AN: 18866

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13804

East Asian (EAS) AF: 0.00 AC: 0 AN: 31100

South Asian (SAS) AF: 0.00 AC: 0 AN: 44940

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32072

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2040

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 313738

Other (OTH) AF: 0.00 AC: 0 AN: 27356

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	2.1
DANN	Benign	0.44
PhyloP100		-1.1
PromoterAI		0.025	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs266719; hg19: chr3-186501648;