rs12139143

Positions:

• chr1-44884356-C-A
• chr1-44884356-C-G

Variant summary

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

The ENST00000360403.7(EIF2B3):​c.657-2617G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 151,936 control chromosomes in the GnomAD database, including 2,696 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 0.18 (2696 hom., cov: 31)
• Consequence: EIF2B3 ENST00000360403.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.368

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF2B3	NM_020365.5	c.657-2617G>T		intron_variant		ENST00000360403.7	NP_065098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF2B3	ENST00000360403.7	c.657-2617G>T		intron_variant		1	NM_020365.5	ENSP00000353575	P1
EIF2B3	ENST00000372183.7	c.657-2617G>T		intron_variant		1		ENSP00000361257
EIF2B3	ENST00000620860.4	c.657-2617G>T		intron_variant		1		ENSP00000483996
EIF2B3	ENST00000439363.5	c.119-2617G>T		intron_variant		3		ENSP00000396985

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27166 AN: 151818 Hom.: 2687 Cov.: 31

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.179 AC: 27193 AN: 151936 Hom.: 2696 Cov.: 31 AF XY: 0.181 AC XY: 13459 AN XY: 74274

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.280

Gnomad4 ASJ AF: 0.156

Gnomad4 EAS AF: 0.277

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.185

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.177

Alfa AF: 0.168 Hom.: 2763

Bravo AF: 0.184

Asia WGS AF: 0.225 AC: 785 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.67
DANN	Benign	0.67

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: rs12139143; hg19: chr1-45350028;