rs1022814

chr1-44948174-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020365.5(EIF2B3):c.295-6509T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 152,276 control chromosomes in the GnomAD database, including 2,299 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (2299 hom., cov: 32)
• Consequence: EIF2B3 NM_020365.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.231

Genes affected

EIF2B3 (HGNC:3259): (eukaryotic translation initiation factor 2B subunit gamma) The protein encoded by this gene is one of the subunits of initiation factor eIF2B, which catalyzes the exchange of eukaryotic initiation factor 2-bound GDP for GTP. It has also been found to function as a cofactor of hepatitis C virus internal ribosome entry site-mediated translation. Mutations in this gene have been associated with leukodystrophy with vanishing white matter. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EIF2B3	NM_020365.5	c.295-6509T>C		intron_variant		ENST00000360403.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EIF2B3	ENST00000360403.7	c.295-6509T>C		intron_variant		1	NM_020365.5	P1

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25794 AN: 152158 Hom.: 2288 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.143

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.170 AC: 25839 AN: 152276 Hom.: 2299 Cov.: 32 AF XY: 0.169 AC XY: 12564 AN XY: 74462

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.169

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.154

Gnomad4 NFE AF: 0.179

Gnomad4 OTH AF: 0.141

Alfa AF: 0.176 Hom.: 730

Bravo AF: 0.171

Asia WGS AF: 0.149 AC: 517 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	5.3
Dann	Benign	0.39

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: rs1022814; hg19: chr1-45413846;