1-44965992-A-G

Position:

• chr1-44965992-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.294+12323T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 151,830 control chromosomes in the GnomAD database, including 6,072 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 0.25 (6072 hom., cov: 29)
• Consequence: EIF2B3 NM_020365.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0420

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF2B3	NM_020365.5	c.294+12323T>C		intron_variant		ENST00000360403.7	NP_065098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF2B3	ENST00000360403.7	c.294+12323T>C		intron_variant		1	NM_020365.5	ENSP00000353575	P1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38242 AN: 151712 Hom.: 6058 Cov.: 29

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.0987

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.205

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

GnomAD4 genome AF: 0.252 AC: 38295 AN: 151830 Hom.: 6072 Cov.: 29 AF XY: 0.249 AC XY: 18481 AN XY: 74202

Gnomad4 AFR AF: 0.456

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.162

Gnomad4 EAS AF: 0.169

Gnomad4 SAS AF: 0.169

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.203

Alfa AF: 0.236 Hom.: 752

Bravo AF: 0.265

Asia WGS AF: 0.167 AC: 579 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.56

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: rs546354; hg19: chr1-45431664;