rs11684404

chr2-88625104-T-C

Variant summary

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

The NM_004836.7(EIF2AK3):c.308+1863A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 152,098 control chromosomes in the GnomAD database, including 7,481 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 0.29 (7481 hom., cov: 32)
• Consequence: EIF2AK3 NM_004836.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00400

Genes affected

EIF2AK3 (HGNC:3255): (eukaryotic translation initiation factor 2 alpha kinase 3) The protein encoded by this gene phosphorylates the alpha subunit of eukaryotic translation-initiation factor 2, leading to its inactivation, and thus to a rapid reduction of translational initiation and repression of global protein synthesis. This protein is thought to modulate mitochondrial function. It is a type I membrane protein located in the endoplasmic reticulum (ER), where it is induced by ER stress caused by malfolded proteins. Mutations in this gene are associated with Wolcott-Rallison syndrome. [provided by RefSeq, Sep 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EIF2AK3	NM_004836.7	c.308+1863A>G		intron_variant		ENST00000303236.9
EIF2AK3	XM_047446428.1	c.17+2585A>G		intron_variant
EIF2AK3	XM_047446430.1	c.308+1863A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EIF2AK3	ENST00000303236.9	c.308+1863A>G		intron_variant		1	NM_004836.7	P1
EIF2AK3	ENST00000682892.1	c.-145-11251A>G		intron_variant
EIF2AK3	ENST00000652099.1	c.306+1863A>G		intron_variant, NMD_transcript_variant
EIF2AK3	ENST00000652423.1	c.184+1863A>G		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43763 AN: 151980 Hom.: 7471 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.320

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

GnomAD4 genome AF: 0.288 AC: 43786 AN: 152098 Hom.: 7481 Cov.: 32 AF XY: 0.296 AC XY: 22026 AN XY: 74338

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.375

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.509

Gnomad4 SAS AF: 0.473

Gnomad4 FIN AF: 0.408

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.323

Alfa AF: 0.319 Hom.: 4084

Bravo AF: 0.275

Asia WGS AF: 0.434 AC: 1508 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	3.1
Dann	Benign	0.34

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: rs11684404; hg19: chr2-88924622;