3-184135287-G-A

Position:

• chr3-184135287-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000491144.5(EIF2B5):​n.250G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00233 in 1,492,528 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0028 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0023 (19 hom.)
• Consequence: EIF2B5 ENST00000491144.5 non_coding_transcript_exon
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.09

Genes affected

EIF2B5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BS2: High Homozygotes in GnomAdExome4 at 19 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.184135287G>A		intergenic_region
EIF2B5-DT	NR_183718.1	n.-26C>T		upstream_gene_variant
EIF2B5-DT	NR_183719.1	n.-26C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF2B5	ENST00000491144.5	n.250G>A		non_coding_transcript_exon_variant	1/15	2
EIF2B5-DT	ENST00000608135.1	n.-49C>T		upstream_gene_variant		5
EIF2B5	ENST00000649814.1	n.-50G>A		upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.00284 AC: 432 AN: 152208 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0122

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00370

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00228 AC: 3053 AN: 1340202 Hom.: 19 Cov.: 22 AF XY: 0.00241 AC XY: 1596 AN XY: 663560

Gnomad4 AFR exome AF: 0.000197

Gnomad4 AMR exome AF: 0.000396

Gnomad4 ASJ exome AF: 0.0101

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0120

Gnomad4 NFE exome AF: 0.00204

Gnomad4 OTH exome AF: 0.00198

GnomAD4 genome AF: 0.00284 AC: 432 AN: 152326 Hom.: 1 Cov.: 33 AF XY: 0.00316 AC XY: 235 AN XY: 74470

Gnomad4 AFR AF: 0.000240

Gnomad4 AMR AF: 0.000261

Gnomad4 ASJ AF: 0.0104

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0122

Gnomad4 NFE AF: 0.00370

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00387 Hom.: 1

Bravo AF: 0.00149

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.023
DANN	Benign	0.80

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: rs137921645; hg19: chr3-183853075;