15-39991049-T-C

Variant names:

• chr15-39991049-T-C
• rs16970137
• NM_001013703.4:c.2631+672T>C

Variant summary

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

The NM_001013703.4(EIF2AK4):​c.2631+672T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 152,444 control chromosomes in the GnomAD database, including 22,900 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 0.53 (22819 hom., cov: 33)
  • Exomes 𝑓: 0.65 (81 hom.)
• Consequence: EIF2AK4 NM_001013703.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.401

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF2AK4	NM_001013703.4	c.2631+672T>C		intron_variant	Intron 16 of 38	ENST00000263791.10	NP_001013725.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF2AK4	ENST00000263791.10	c.2631+672T>C		intron_variant	Intron 16 of 38	2	NM_001013703.4	ENSP00000263791.5
EIF2AK4	ENST00000560855.5	c.1962+672T>C		intron_variant	Intron 11 of 33	5		ENSP00000453575.1
EIF2AK4	ENST00000558629.5	n.-117T>C		upstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.530 AC: 80517 AN: 151956 Hom.: 22815 Cov.: 33

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.646

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.520

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.568

GnomAD4 exome AF: 0.649 AC: 240 AN: 370 Hom.: 81 AF XY: 0.643 AC XY: 148 AN XY: 230

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.750

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.617

Gnomad4 NFE exome AF: 0.675

Gnomad4 OTH exome AF: 0.556

GnomAD4 genome AF: 0.530 AC: 80560 AN: 152074 Hom.: 22819 Cov.: 33 AF XY: 0.529 AC XY: 39314 AN XY: 74340

Gnomad4 AFR AF: 0.326

Gnomad4 AMR AF: 0.496

Gnomad4 ASJ AF: 0.685

Gnomad4 EAS AF: 0.519

Gnomad4 SAS AF: 0.497

Gnomad4 FIN AF: 0.596

Gnomad4 NFE AF: 0.644

Gnomad4 OTH AF: 0.562

Alfa AF: 0.622 Hom.: 32384

Bravo AF: 0.517

Asia WGS AF: 0.473 AC: 1643 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.8
DANN	Benign	0.67

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: rs16970137; hg19: chr15-40283250;