14-75009191-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.254

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]

ACMG classification

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 GnomAd at 59 AR gene

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EIF2B2	ENST00000266126.10	c.*3G>C		3_prime_UTR_variant	8/8	1	NM_014239.4	P1
EIF2B2	ENST00000556668.1	n.639G>C		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.0210 AC: 3193 AN: 151986 Hom.: 59 Cov.: 32

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.: 48 AF XY: 0.0158 AC XY: 2149 AN XY: 135886

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.: 32 AF XY: 0.0137 AC XY: 9949 AN XY: 727166

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.: 60 Cov.: 32 AF XY: 0.0205 AC XY: 1527 AN XY: 74348

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.: 4

Bravo AF: 0.0220

Asia WGS AF: 0.0290 AC: 99 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

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

- -

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

Other links and lift over

dbSNP: rs112087431; hg19: chr14-75475894;