rs7298287

chr12-123627176-T-Cchr12-123627176-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001414.4(EIF2B1):c.370-20A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0909 in 1,603,222 control chromosomes in the GnomAD database, including 13,539 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (5082 hom., cov: 32)
  • Exomes 𝑓: 0.081 (8457 hom.)
• Consequence: EIF2B1 NM_001414.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -4.54

Genes affected

EIF2B1 (HGNC:3257): (eukaryotic translation initiation factor 2B subunit alpha) This gene encodes one of five subunits of eukaryotic translation initiation factor 2B (EIF2B), a GTP exchange factor for eukaryotic initiation factor 2 and an essential regulator for protein synthesis. Mutations in this gene and the genes encoding other EIF2B subunits have been associated with leukoencephalopathy with vanishing white matter. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 12-123627176-T-C is Benign according to our data. Variant chr12-123627176-T-C is described in ClinVar as [Benign]. Clinvar id is 93731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EIF2B1	NM_001414.4	c.370-20A>G		intron_variant		ENST00000424014.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EIF2B1	ENST00000424014.7	c.370-20A>G		intron_variant		1	NM_001414.4	P1
EIF2B1	ENST00000534960.5	c.417-2314A>G		intron_variant		5
EIF2B1	ENST00000537073.1	c.370-20A>G		intron_variant		2
EIF2B1	ENST00000539951.5	c.331-20A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28208 AN: 151924 Hom.: 5036 Cov.: 32

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.0698

Gnomad EAS AF: 0.0931

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.0516

Gnomad MID AF: 0.0892

Gnomad NFE AF: 0.0641

Gnomad OTH AF: 0.149

GnomAD3 exomes AF: 0.108 AC: 27245 AN: 251366 Hom.: 2912 AF XY: 0.103 AC XY: 14026 AN XY: 135866

Gnomad AFR exome AF: 0.488

Gnomad AMR exome AF: 0.0806

Gnomad ASJ exome AF: 0.0690

Gnomad EAS exome AF: 0.0983

Gnomad SAS exome AF: 0.159

Gnomad FIN exome AF: 0.0548

Gnomad NFE exome AF: 0.0657

Gnomad OTH exome AF: 0.0831

GnomAD4 exome AF: 0.0809 AC: 117442 AN: 1451180 Hom.: 8457 Cov.: 28 AF XY: 0.0822 AC XY: 59389 AN XY: 722584

Gnomad4 AFR exome AF: 0.486

Gnomad4 AMR exome AF: 0.0875

Gnomad4 ASJ exome AF: 0.0681

Gnomad4 EAS exome AF: 0.0750

Gnomad4 SAS exome AF: 0.159

Gnomad4 FIN exome AF: 0.0532

Gnomad4 NFE exome AF: 0.0632

Gnomad4 OTH exome AF: 0.0999

GnomAD4 genome AF: 0.186 AC: 28316 AN: 152042 Hom.: 5082 Cov.: 32 AF XY: 0.184 AC XY: 13654 AN XY: 74328

Gnomad4 AFR AF: 0.473

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.0698

Gnomad4 EAS AF: 0.0923

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.0516

Gnomad4 NFE AF: 0.0641

Gnomad4 OTH AF: 0.157

Alfa AF: 0.0893 Hom.: 1506

Bravo AF: 0.202

Asia WGS AF: 0.173 AC: 602 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 09, 2012	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.0020
Dann	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs7298287; hg19: chr12-124111723; COSMIC: COSV71194412; COSMIC: COSV71194412;