7-6027612-T-C

Position:

• chr7-6027612-T-C

Variant summary

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

The NM_014413.4(EIF2AK1):​c.1531-651A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 151,864 control chromosomes in the GnomAD database, including 7,422 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 0.29 (7422 hom., cov: 31)
• Consequence: EIF2AK1 NM_014413.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.216

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF2AK1	NM_014413.4	c.1531-651A>G		intron_variant		ENST00000199389.11	NP_055228.2
EIF2AK1	NM_001134335.2	c.1528-651A>G		intron_variant			NP_001127807.1
EIF2AK1	XM_047420200.1	c.907-651A>G		intron_variant			XP_047276156.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF2AK1	ENST00000199389.11	c.1531-651A>G		intron_variant		1	NM_014413.4	ENSP00000199389.6
EIF2AK1	ENST00000490523.1	n.226-651A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44000 AN: 151746 Hom.: 7408 Cov.: 31

Gnomad AFR AF: 0.448

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.257

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.290 AC: 44041 AN: 151864 Hom.: 7422 Cov.: 31 AF XY: 0.292 AC XY: 21693 AN XY: 74234

Gnomad4 AFR AF: 0.448

Gnomad4 AMR AF: 0.255

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.493

Gnomad4 SAS AF: 0.289

Gnomad4 FIN AF: 0.239

Gnomad4 NFE AF: 0.203

Gnomad4 OTH AF: 0.265

Alfa AF: 0.161 Hom.: 410

Bravo AF: 0.296

Asia WGS AF: 0.399 AC: 1386 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.2
DANN	Benign	0.77

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: rs10487933; hg19: chr7-6067243;