rs7298287

Variant names:

• chr12-123627176-T-C
• rs7298287
• NM_001414.4:c.370-20A>G

Your query was ambiguous. Multiple possible variants found:

• chr12-123627176-T-C
• chr12-123627176-T-G

Variant summary

Our verdict is Benign. The variant received -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:4
• Conservation: PhyloP100: -4.54
• Publications: 8 publications found

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]

EIF2B1 Gene-Disease associations (from GenCC):

• leukoencephalopathy with vanishing white matter

  Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
• leukoencephalopathy with vanishing white matter 1

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• ovarioleukodystrophy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
EIF2B1	NM_001414.4	c.370-20A>G		intron_variant	Intron 4 of 8	ENST00000424014.7	NP_001405.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF2B1	ENST00000424014.7	c.370-20A>G		intron_variant	Intron 4 of 8	1	NM_001414.4	ENSP00000416250.2
EIF2B1	ENST00000537073.1	c.370-20A>G		intron_variant	Intron 4 of 4	2		ENSP00000444183.1
EIF2B1	ENST00000539951.5	c.331-20A>G		intron_variant	Intron 3 of 6	5		ENSP00000438060.1
EIF2B1	ENST00000534960.5	c.415-2314A>G		intron_variant	Intron 4 of 5	5		ENSP00000443172.1

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

GnomAD2 exomes AF: 0.108 AC: 27245 AN: 251366 AF XY: 0.103

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 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

African (AFR) AF: 0.486 AC: 16199 AN: 33308

American (AMR) AF: 0.0875 AC: 3911 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0681 AC: 1775 AN: 26072

East Asian (EAS) AF: 0.0750 AC: 2973 AN: 39660

South Asian (SAS) AF: 0.159 AC: 13645 AN: 85958

European-Finnish (FIN) AF: 0.0532 AC: 2839 AN: 53378

Middle Eastern (MID) AF: 0.0842 AC: 425 AN: 5046

European-Non Finnish (NFE) AF: 0.0632 AC: 69680 AN: 1103056

Other (OTH) AF: 0.0999 AC: 5995 AN: 59986

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

African (AFR) AF: 0.473 AC: 19586 AN: 41412

American (AMR) AF: 0.130 AC: 1984 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0698 AC: 242 AN: 3468

East Asian (EAS) AF: 0.0923 AC: 477 AN: 5166

South Asian (SAS) AF: 0.151 AC: 728 AN: 4810

European-Finnish (FIN) AF: 0.0516 AC: 547 AN: 10596

Middle Eastern (MID) AF: 0.0925 AC: 27 AN: 292

European-Non Finnish (NFE) AF: 0.0641 AC: 4358 AN: 67998

Other (OTH) AF: 0.157 AC: 332 AN: 2112

Alfa AF: 0.103 Hom.: 3158

Bravo AF: 0.202

Asia WGS AF: 0.173 AC: 602 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Aug 09, 2012

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.0020
DANN	Benign	0.47
PhyloP100		-4.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7298287; hg19: chr12-124111723; COSMIC: COSV71194412; COSMIC: COSV71194412;