Variant 14-75009191-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_014239.4(EIF2B2):c.*3G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0138 in 1,613,784 control chromosomes in the GnomAD database, including 260 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 60 hom., cov: 32)

Exomes 𝑓: 0.013 ( 200 hom. )

Consequence

EIF2B2
NM_014239.4 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.254

Variant links:

Genes affected

EIF2B2 (HGNC:3258): (eukaryotic translation initiation factor 2B subunit beta) This gene encodes the beta subunit of eukaryotic initiation factor-2B (EIF2B). EIF2B is involved in protein synthesis and exchanges GDP and GTP for its activation and deactivation. [provided by RefSeq, Aug 2011]

EIF2B2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 14-75009191-G-C is Benign according to our data. Variant chr14-75009191-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 260364.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.021 (3201/152102) while in subpopulation AFR AF= 0.0461 (1910/41466). AF 95% confidence interval is 0.0443. There are 60 homozygotes in gnomad4. There are 1527 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 60 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF2B2	NM_014239.4 link	c.*3G>C		3_prime_UTR_variant	8/8	ENST00000266126.10	NP_055054.1	P49770Q53XC2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF2B2	ENST00000266126.10 link	c.*3G>C		3_prime_UTR_variant	8/8	1	NM_014239.4	ENSP00000266126.5		P49770
EIF2B2	ENST00000556668.1 link	n.639G>C		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.0210

AC:

3193

AN:

151986

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0460

Gnomad AMI

AF:

0.0209

Gnomad AMR

AF:

0.0119

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.0102

Gnomad SAS

AF:

0.0415

Gnomad FIN

AF:

0.00161

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0111

Gnomad OTH

AF:

0.0182

GnomAD3 exomes

AF:

0.0150

AC:

3759

AN:

251416

Hom.:

AF XY:

0.0158

AC XY:

2149

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.0435

Gnomad AMR exome

AF:

0.00818

Gnomad ASJ exome

AF:

0.00347

Gnomad EAS exome

AF:

0.0122

Gnomad SAS exome

AF:

0.0380

Gnomad FIN exome

AF:

0.00162

Gnomad NFE exome

AF:

0.0107

Gnomad OTH exome

AF:

0.0148

GnomAD4 exome

AF:

0.0130

AC:

19068

AN:

1461682

Hom.:

200

Cov.:

AF XY:

0.0137

AC XY:

9949

AN XY:

727166

show subpopulations

Gnomad4 AFR exome

AF:

0.0477

Gnomad4 AMR exome

AF:

0.00841

Gnomad4 ASJ exome

AF:

0.00436

Gnomad4 EAS exome

AF:

0.0101

Gnomad4 SAS exome

AF:

0.0365

Gnomad4 FIN exome

AF:

0.00165

Gnomad4 NFE exome

AF:

0.0110

Gnomad4 OTH exome

AF:

0.0152

GnomAD4 genome

AF:

0.0210

AC:

3201

AN:

152102

Hom.:

Cov.:

AF XY:

0.0205

AC XY:

1527

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0461

Gnomad4 AMR

AF:

0.0118

Gnomad4 ASJ

AF:

0.00519

Gnomad4 EAS

AF:

0.0102

Gnomad4 SAS

AF:

0.0415

Gnomad4 FIN

AF:

0.00161

Gnomad4 NFE

AF:

0.0111

Gnomad4 OTH

AF:

0.0180

Alfa

AF:

0.00811

Hom.:

Bravo

AF:

0.0220

Asia WGS

AF:

0.0290

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 31, 2017	- -
Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Lynch syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Vanishing white matter disease

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.39

DANN

Benign

0.53

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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