rs11211044

Positions:

• chr1-44853080-C-T

Variant summary

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

The NM_020365.5(EIF2B3):​c.1307-2077G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 151,772 control chromosomes in the GnomAD database, including 14,924 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 0.43 (14924 hom., cov: 30)
• Consequence: EIF2B3 NM_020365.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF2B3	NM_020365.5	c.1307-2077G>A		intron_variant		ENST00000360403.7	NP_065098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF2B3	ENST00000360403.7	c.1307-2077G>A		intron_variant		1	NM_020365.5	ENSP00000353575.2
EIF2B3	ENST00000620860.4	c.1203-2077G>A		intron_variant		1		ENSP00000483996.1
EIF2B3	ENST00000439363.5	c.663-2077G>A		intron_variant		3		ENSP00000396985.1

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65224 AN: 151654 Hom.: 14894 Cov.: 30

Gnomad AFR AF: 0.587

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.381

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

GnomAD4 genome AF: 0.430 AC: 65314 AN: 151772 Hom.: 14924 Cov.: 30 AF XY: 0.429 AC XY: 31848 AN XY: 74188

Gnomad4 AFR AF: 0.587

Gnomad4 AMR AF: 0.468

Gnomad4 ASJ AF: 0.320

Gnomad4 EAS AF: 0.447

Gnomad4 SAS AF: 0.346

Gnomad4 FIN AF: 0.339

Gnomad4 NFE AF: 0.355

Gnomad4 OTH AF: 0.381

Alfa AF: 0.376 Hom.: 7218

Bravo AF: 0.448

Asia WGS AF: 0.390 AC: 1354 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.82
DANN	Benign	0.74

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: rs11211044; hg19: chr1-45318752;