15-39939299-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001013703.4(EIF2AK4):c.145-206A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 152,088 control chromosomes in the GnomAD database, including 10,118 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.34 (10118 hom., cov: 33)
• Consequence: EIF2AK4 NM_001013703.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.989

Genes affected

EIF2AK4 (HGNC:19687): (eukaryotic translation initiation factor 2 alpha kinase 4) This gene encodes a member of a family of kinases that phosphorylate the alpha subunit of eukaryotic translation initiation factor-2 (EIF2), resulting in the downregulaton of protein synthesis. The encoded protein responds to amino acid deprivation by binding uncharged transfer RNAs. It may also be activated by glucose deprivation and viral infection. Mutations in this gene have been found in individuals suffering from autosomal recessive pulmonary venoocclusive-disease-2. [provided by RefSeq, Mar 2014]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 15-39939299-A-G is Benign according to our data. Variant chr15-39939299-A-G is described in ClinVar as [Benign]. Clinvar id is 674659.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EIF2AK4	NM_001013703.4	c.145-206A>G		intron_variant		ENST00000263791.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EIF2AK4	ENST00000263791.10	c.145-206A>G		intron_variant		2	NM_001013703.4	P1
EIF2AK4	ENST00000559624.5	c.145-206A>G		intron_variant		1
EIF2AK4	ENST00000560648.1	c.145-206A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52209 AN: 151968 Hom.: 10102 Cov.: 33

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.805

Gnomad SAS AF: 0.562

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.344 AC: 52271 AN: 152088 Hom.: 10118 Cov.: 33 AF XY: 0.354 AC XY: 26309 AN XY: 74324

Gnomad4 AFR AF: 0.373

Gnomad4 AMR AF: 0.459

Gnomad4 ASJ AF: 0.302

Gnomad4 EAS AF: 0.806

Gnomad4 SAS AF: 0.562

Gnomad4 FIN AF: 0.300

Gnomad4 NFE AF: 0.259

Gnomad4 OTH AF: 0.355

Alfa AF: 0.290 Hom.: 1414

Bravo AF: 0.357

Asia WGS AF: 0.651 AC: 2263 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	4.7
Dann	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.27		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.27		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs525910; hg19: chr15-40231500;