rs3207297

Positions:

chr15-40020940-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001013703.4(EIF2AK4):c.4215C>T(p.Gly1405Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 1,611,428 control chromosomes in the GnomAD database, including 101,120 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 9232 hom., cov: 31)

Exomes 𝑓: 0.35 ( 91888 hom. )

Consequence

EIF2AK4
NM_001013703.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.0170

Variant links:

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]

EIF2AK4 links:

EIF2AK4 (HGNC:):

EIF2AK4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.28).

BP6

Variant 15-40020940-C-T is Benign according to our data. Variant chr15-40020940-C-T is described in ClinVar as [Benign]. Clinvar id is 381184.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-40020940-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.017 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF2AK4	NM_001013703.4 linkuse as main transcript	c.4215C>T	p.Gly1405Gly	synonymous_variant	31/39	ENST00000263791.10	NP_001013725.2	Q9P2K8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF2AK4	ENST00000263791.10 linkuse as main transcript	c.4215C>T	p.Gly1405Gly	synonymous_variant	31/39	2	NM_001013703.4	ENSP00000263791.5		Q9P2K8-1

Frequencies

GnomAD3 genomes

AF:

0.349

AC:

52926

AN:

151696

Hom.:

9225

Cov.:

show subpopulations

Gnomad AFR

AF:

0.340

Gnomad AMI

AF:

0.466

Gnomad AMR

AF:

0.327

Gnomad ASJ

AF:

0.366

Gnomad EAS

AF:

0.255

Gnomad SAS

AF:

0.362

Gnomad FIN

AF:

0.331

Gnomad MID

AF:

0.396

Gnomad NFE

AF:

0.364

Gnomad OTH

AF:

0.381

GnomAD3 exomes

AF:

0.341

AC:

84664

AN:

248142

Hom.:

14894

AF XY:

0.346

AC XY:

46532

AN XY:

134648

show subpopulations

Gnomad AFR exome

AF:

0.340

Gnomad AMR exome

AF:

0.283

Gnomad ASJ exome

AF:

0.366

Gnomad EAS exome

AF:

0.244

Gnomad SAS exome

AF:

0.373

Gnomad FIN exome

AF:

0.330

Gnomad NFE exome

AF:

0.364

Gnomad OTH exome

AF:

0.364

GnomAD4 exome

AF:

0.353

AC:

515927

AN:

1459612

Hom.:

91888

Cov.:

AF XY:

0.355

AC XY:

257867

AN XY:

726128

show subpopulations

Gnomad4 AFR exome

AF:

0.337

Gnomad4 AMR exome

AF:

0.290

Gnomad4 ASJ exome

AF:

0.375

Gnomad4 EAS exome

AF:

0.285

Gnomad4 SAS exome

AF:

0.380

Gnomad4 FIN exome

AF:

0.331

Gnomad4 NFE exome

AF:

0.357

Gnomad4 OTH exome

AF:

0.358

GnomAD4 genome

AF:

0.349

AC:

52951

AN:

151816

Hom.:

9232

Cov.:

AF XY:

0.347

AC XY:

25758

AN XY:

74194

show subpopulations

Gnomad4 AFR

AF:

0.340

Gnomad4 AMR

AF:

0.328

Gnomad4 ASJ

AF:

0.366

Gnomad4 EAS

AF:

0.254

Gnomad4 SAS

AF:

0.362

Gnomad4 FIN

AF:

0.331

Gnomad4 NFE

AF:

0.364

Gnomad4 OTH

AF:

0.376

Alfa

AF:

0.364

Hom.:

23796

Bravo

AF:

0.348

Asia WGS

AF:

0.294

AC:

1025

AN:

3478

EpiCase

AF:

0.378

EpiControl

AF:

0.375

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 03, 2016	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. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Familial pulmonary capillary hemangiomatosis

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.28

CADD

Benign

9.8

DANN

Benign

0.69

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over