Variant chr15-39934184-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001013703.4(EIF2AK4):c.-12C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00163 in 1,514,278 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0090 ( 25 hom., cov: 33)

Exomes 𝑓: 0.00080 ( 12 hom. )

Consequence

EIF2AK4
NM_001013703.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.236

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 15-39934184-C-A is Benign according to our data. Variant chr15-39934184-C-A is described in ClinVar as [Benign]. Clinvar id is 993783.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00905 (1376/152126) while in subpopulation AFR AF= 0.031 (1286/41540). AF 95% confidence interval is 0.0296. There are 25 homozygotes in gnomad4. There are 622 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF2AK4	NM_001013703.4 linkuse as main transcript	c.-12C>A		5_prime_UTR_variant	1/39	ENST00000263791.10	NP_001013725.2

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF2AK4	ENST00000263791.10 linkuse as main transcript	c.-12C>A	5_prime_UTR_variant	1/39	2	NM_001013703.4	ENSP00000263791	P1	Q9P2K8-1
EIF2AK4	ENST00000559624.5 linkuse as main transcript	c.-12C>A	5_prime_UTR_variant	1/11	1		ENSP00000453148		Q9P2K8-3
EIF2AK4	ENST00000560648.1 linkuse as main transcript	c.-12C>A	5_prime_UTR_variant	1/4	3		ENSP00000453968

Frequencies

GnomAD3 genomes

AF:

0.00900

AC:

1368

AN:

152014

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0308

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00406

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00767

GnomAD3 exomes

AF:

0.00174

AC:

206

AN:

118704

Hom.:

AF XY:

0.00139

AC XY:

AN XY:

66178

show subpopulations

Gnomad AFR exome

AF:

0.0396

Gnomad AMR exome

AF:

0.00176

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000960

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000111

Gnomad OTH exome

AF:

0.000883

GnomAD4 exome

AF:

0.000801

AC:

1091

AN:

1362152

Hom.:

Cov.:

AF XY:

0.000696

AC XY:

468

AN XY:

672638

show subpopulations

Gnomad4 AFR exome

AF:

0.0286

Gnomad4 AMR exome

AF:

0.00271

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000651

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000507

Gnomad4 OTH exome

AF:

0.00181

GnomAD4 genome

AF:

0.00905

AC:

1376

AN:

152126

Hom.:

Cov.:

AF XY:

0.00836

AC XY:

622

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.0310

Gnomad4 AMR

AF:

0.00399

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00759

Alfa

AF:

0.00424

Hom.:

Bravo

AF:

0.00977

Asia WGS

AF:

0.00202

AC:

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Familial pulmonary capillary hemangiomatosis

Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Sep 13, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

8.7

DANN

Benign

0.89

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

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

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