15-39943351-CT-C

Variant summary

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

The NM_001013703.4(EIF2AK4):c.258-12del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.098 (247 hom., cov: 0)
  • Exomes 𝑓: 0.18 (31 hom.)
• Consequence: EIF2AK4 NM_001013703.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.595

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 15-39943351-CT-C is Benign according to our data. Variant chr15-39943351-CT-C is described in ClinVar as [Benign]. Clinvar id is 1292297.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EIF2AK4	NM_001013703.4	c.258-12del		intron_variant		ENST00000263791.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EIF2AK4	ENST00000263791.10	c.258-12del		intron_variant		2	NM_001013703.4	P1
EIF2AK4	ENST00000559624.5	c.258-12del		intron_variant		1
EIF2AK4	ENST00000560648.1	c.258-12del		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0984 AC: 10469 AN: 106402 Hom.: 245 Cov.: 0

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.0924

Gnomad AMR AF: 0.0812

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.288

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.0673

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0681

Gnomad OTH AF: 0.0878

GnomAD3 exomes AF: 0.122 AC: 4571 AN: 37334 Hom.: 11 AF XY: 0.118 AC XY: 2421 AN XY: 20570

Gnomad AFR exome AF: 0.128

Gnomad AMR exome AF: 0.0980

Gnomad ASJ exome AF: 0.117

Gnomad EAS exome AF: 0.0849

Gnomad SAS exome AF: 0.0611

Gnomad FIN exome AF: 0.0777

Gnomad NFE exome AF: 0.144

Gnomad OTH exome AF: 0.122

GnomAD4 exome AF: 0.184 AC: 137883 AN: 750810 Hom.: 31 Cov.: 0 AF XY: 0.178 AC XY: 68267 AN XY: 384490

Gnomad4 AFR exome AF: 0.178

Gnomad4 AMR exome AF: 0.0818

Gnomad4 ASJ exome AF: 0.161

Gnomad4 EAS exome AF: 0.200

Gnomad4 SAS exome AF: 0.106

Gnomad4 FIN exome AF: 0.126

Gnomad4 NFE exome AF: 0.196

Gnomad4 OTH exome AF: 0.187

GnomAD4 genome AF: 0.0985 AC: 10475 AN: 106388 Hom.: 247 Cov.: 0 AF XY: 0.101 AC XY: 5050 AN XY: 49952

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.0813

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.288

Gnomad4 SAS AF: 0.147

Gnomad4 FIN AF: 0.0673

Gnomad4 NFE AF: 0.0681

Gnomad4 OTH AF: 0.0901

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 09, 2020

- -

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: rs5812147; hg19: chr15-40235552;