rs558030

chr7-6058036-T-A

Variant summary

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

The NM_014413.4(EIF2AK1):c.118+930A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 416,280 control chromosomes in the GnomAD database, including 31,106 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 0.35 (10196 hom., cov: 31)
  • Exomes 𝑓: 0.39 (20910 hom.)
• Consequence: EIF2AK1 NM_014413.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.452

Genes affected

EIF2AK1 (HGNC:24921): (eukaryotic translation initiation factor 2 alpha kinase 1) The protein encoded by this gene acts at the level of translation initiation to downregulate protein synthesis in response to stress. The encoded protein is a kinase that can be inactivated by hemin. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EIF2AK1	NM_014413.4	c.118+930A>T		intron_variant		ENST00000199389.11
EIF2AK1	NM_001134335.2	c.118+930A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EIF2AK1	ENST00000199389.11	c.118+930A>T		intron_variant		1	NM_014413.4	P1

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53194 AN: 151830 Hom.: 10191 Cov.: 31

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.369

GnomAD4 exome AF: 0.393 AC: 103888 AN: 264332 Hom.: 20910 AF XY: 0.393 AC XY: 59280 AN XY: 150946

Gnomad4 AFR exome AF: 0.204

Gnomad4 AMR exome AF: 0.327

Gnomad4 ASJ exome AF: 0.442

Gnomad4 EAS exome AF: 0.379

Gnomad4 SAS exome AF: 0.350

Gnomad4 FIN exome AF: 0.342

Gnomad4 NFE exome AF: 0.428

Gnomad4 OTH exome AF: 0.393

GnomAD4 genome AF: 0.350 AC: 53209 AN: 151948 Hom.: 10196 Cov.: 31 AF XY: 0.346 AC XY: 25714 AN XY: 74262

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.365

Gnomad4 ASJ AF: 0.437

Gnomad4 EAS AF: 0.378

Gnomad4 SAS AF: 0.347

Gnomad4 FIN AF: 0.349

Gnomad4 NFE AF: 0.430

Gnomad4 OTH AF: 0.366

Alfa AF: 0.386 Hom.: 1516

Bravo AF: 0.345

Asia WGS AF: 0.316 AC: 1101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	9.0
Dann	Benign	0.88

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: rs558030; hg19: chr7-6097667;