rs7176881

Positions:

• chr15-39974635-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000559624.5(EIF2AK4):​c.*853C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,226 control chromosomes in the GnomAD database, including 962 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.11 (962 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: EIF2AK4 ENST00000559624.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF2AK4	NM_001013703.4	c.1818+886C>T		intron_variant		ENST00000263791.10	NP_001013725.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF2AK4	ENST00000559624.5	c.*853C>T		3_prime_UTR_variant	11/11	1		ENSP00000453148.1
EIF2AK4	ENST00000263791.10	c.1818+886C>T		intron_variant		2	NM_001013703.4	ENSP00000263791.5
EIF2AK4	ENST00000560855.5	c.1233+886C>T		intron_variant		5		ENSP00000453575.1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16384 AN: 152108 Hom.: 962 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.0890

Gnomad AMR AF: 0.0938

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.0638

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.0835

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.113

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.108 AC: 16384 AN: 152226 Hom.: 962 Cov.: 32 AF XY: 0.111 AC XY: 8235 AN XY: 74430

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.0936

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.0636

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.0835

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.112

Alfa AF: 0.117 Hom.: 558

Bravo AF: 0.104

Asia WGS AF: 0.119 AC: 414 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.8
DANN	Benign	0.47

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: rs7176881; hg19: chr15-40266836;