15-39939914-G-GA

Position:

• chr15-39939914-G-GA

Variant summary

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

The NM_001013703.4(EIF2AK4):​c.257+301dup variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.42 (16261 hom., cov: 0)
• Consequence: EIF2AK4 NM_001013703.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.132

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 15-39939914-G-GA is Benign according to our data. Variant chr15-39939914-G-GA is described in ClinVar as [Benign]. Clinvar id is 672385.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EIF2AK4	NM_001013703.4	c.257+301dup		intron_variant		ENST00000263791.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EIF2AK4	ENST00000263791.10	c.257+301dup		intron_variant		2	NM_001013703.4	P1
EIF2AK4	ENST00000559624.5	c.257+301dup		intron_variant		1
EIF2AK4	ENST00000560648.1	c.257+301dup		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.422 AC: 64150 AN: 151892 Hom.: 16216 Cov.: 0

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.210

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.845

Gnomad SAS AF: 0.566

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.405

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

GnomAD4 genome AF: 0.423 AC: 64257 AN: 152010 Hom.: 16261 Cov.: 0 AF XY: 0.431 AC XY: 32042 AN XY: 74334

Gnomad4 AFR AF: 0.638

Gnomad4 AMR AF: 0.500

Gnomad4 ASJ AF: 0.303

Gnomad4 EAS AF: 0.846

Gnomad4 SAS AF: 0.566

Gnomad4 FIN AF: 0.300

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.406

Alfa AF: 0.353 Hom.: 1228

Asia WGS AF: 0.683 AC: 2376 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

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: rs35994771; hg19: chr15-40232115;