dbSNP rs78170695: EIF2B1:c.369+50C>T (chr12-123630119-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001414.4(EIF2B1):c.369+50C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00213 in 1,538,694 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.011 ( 39 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 22 hom. )

Consequence

EIF2B1
NM_001414.4 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.118

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 12-123630119-G-A is Benign according to our data. Variant chr12-123630119-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 258090.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0109 (1662/152208) while in subpopulation AFR AF= 0.0378 (1572/41538). AF 95% confidence interval is 0.0363. There are 39 homozygotes in gnomad4. There are 788 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 39 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF2B1	NM_001414.4 link	c.369+50C>T		intron_variant	Intron 4 of 8	ENST00000424014.7	NP_001405.1	Q14232-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF2B1	ENST00000424014.7 link	c.369+50C>T		intron_variant	Intron 4 of 8	1	NM_001414.4	ENSP00000416250.2		Q14232-1

Frequencies

GnomAD3 genomes

AF:

0.0109

AC:

1653

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0377

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00367

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00296

AC:

728

AN:

245864

Hom.:

AF XY:

0.00219

AC XY:

292

AN XY:

133552

show subpopulations

Gnomad AFR exome

AF:

0.0397

Gnomad AMR exome

AF:

0.00154

Gnomad ASJ exome

AF:

0.000504

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000226

Gnomad OTH exome

AF:

0.00199

GnomAD4 exome

AF:

0.00116

AC:

1612

AN:

1386486

Hom.:

Cov.:

AF XY:

0.00101

AC XY:

702

AN XY:

693978

show subpopulations

Gnomad4 AFR exome

AF:

0.0366

Gnomad4 AMR exome

AF:

0.00199

Gnomad4 ASJ exome

AF:

0.000507

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000707

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000171

Gnomad4 OTH exome

AF:

0.00239

GnomAD4 genome

AF:

0.0109

AC:

1662

AN:

152208

Hom.:

Cov.:

AF XY:

0.0106

AC XY:

788

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.0378

Gnomad4 AMR

AF:

0.00367

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00563

Hom.:

Bravo

AF:

0.0125

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.3

DANN

Benign

0.73

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over