rs17720604

chr15-39953725-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001013703.4(EIF2AK4):c.514-179G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,238 control chromosomes in the GnomAD database, including 938 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.11 (938 hom., cov: 33)
• Consequence: EIF2AK4 NM_001013703.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.85

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 15-39953725-G-A is Benign according to our data. Variant chr15-39953725-G-A is described in ClinVar as [Benign]. Clinvar id is 674892.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EIF2AK4	NM_001013703.4	c.514-179G>A		intron_variant		ENST00000263791.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EIF2AK4	ENST00000263791.10	c.514-179G>A		intron_variant		2	NM_001013703.4	P1
EIF2AK4	ENST00000559624.5	c.514-179G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16134 AN: 152120 Hom.: 938 Cov.: 33

Gnomad AFR AF: 0.0925

Gnomad AMI AF: 0.0890

Gnomad AMR AF: 0.0909

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.0570

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.0872

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.106 AC: 16134 AN: 152238 Hom.: 938 Cov.: 33 AF XY: 0.109 AC XY: 8095 AN XY: 74436

Gnomad4 AFR AF: 0.0923

Gnomad4 AMR AF: 0.0908

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.0567

Gnomad4 SAS AF: 0.221

Gnomad4 FIN AF: 0.0872

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.108

Alfa AF: 0.113 Hom.: 1032

Bravo AF: 0.101

Asia WGS AF: 0.117 AC: 406 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	-0.91
Cadd	Benign	0.021
Dann	Benign	0.63

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: rs17720604; hg19: chr15-40245926;