rs558030

Variant names:

• chr7-6058036-T-A
• rs558030
• NM_014413.4:c.118+930A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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]

EIF2AK1 Gene-Disease associations (from GenCC):

• leukoencephalopathy, motor delay, spasticity, and dysarthria syndrome

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014413.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF2AK1	NM_014413.4	MANE Select	c.118+930A>T		intron	N/A	NP_055228.2
	EIF2AK1	NM_001134335.2		c.118+930A>T		intron	N/A	NP_001127807.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF2AK1	ENST00000199389.11	TSL:1 MANE Select	c.118+930A>T		intron	N/A	ENSP00000199389.6
	EIF2AK1	ENST00000446699.1	TSL:4	c.118+930A>T		intron	N/A	ENSP00000397590.1
	EIF2AK1	ENST00000431744.5	TSL:3	n.213+112A>T		intron	N/A	ENSP00000392459.1

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

African (AFR) AF: 0.204 AC: 1332 AN: 6536

American (AMR) AF: 0.327 AC: 6024 AN: 18408

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 3755 AN: 8500

East Asian (EAS) AF: 0.379 AC: 3291 AN: 8692

South Asian (SAS) AF: 0.350 AC: 18795 AN: 53692

European-Finnish (FIN) AF: 0.342 AC: 3948 AN: 11546

Middle Eastern (MID) AF: 0.457 AC: 1108 AN: 2426

European-Non Finnish (NFE) AF: 0.428 AC: 60759 AN: 142118

Other (OTH) AF: 0.393 AC: 4876 AN: 12414

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

African (AFR) AF: 0.202 AC: 8361 AN: 41476

American (AMR) AF: 0.365 AC: 5554 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 1515 AN: 3466

East Asian (EAS) AF: 0.378 AC: 1956 AN: 5178

South Asian (SAS) AF: 0.347 AC: 1667 AN: 4810

European-Finnish (FIN) AF: 0.349 AC: 3674 AN: 10542

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.430 AC: 29216 AN: 67932

Other (OTH) AF: 0.366 AC: 772 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	9.0
DANN	Benign	0.88
PhyloP100		0.45
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs558030; hg19: chr7-6097667;