19-3976323-T-G

Position:

• chr19-3976323-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001961.4(EEF2):​c.*231A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 278,106 control chromosomes in the GnomAD database, including 9,263 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (7626 hom., cov: 31)
  • Exomes 𝑓: 0.13 (1637 hom.)
• Consequence: EEF2 NM_001961.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.874

Genes affected

EEF2 (HGNC:3214): (eukaryotic translation elongation factor 2) This gene encodes a member of the GTP-binding translation elongation factor family. This protein is an essential factor for protein synthesis. It promotes the GTP-dependent translocation of the nascent protein chain from the A-site to the P-site of the ribosome. This protein is completely inactivated by EF-2 kinase phosporylation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 19-3976323-T-G is Benign according to our data. Variant chr19-3976323-T-G is described in ClinVar as [Benign]. Clinvar id is 1292369.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EEF2	NM_001961.4	c.*231A>C		3_prime_UTR_variant	15/15	ENST00000309311.7	NP_001952.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EEF2	ENST00000309311	c.*231A>C		3_prime_UTR_variant	15/15	5	NM_001961.4	ENSP00000307940.5
EEF2	ENST00000600794.1	c.107-23A>C		intron_variant		3		ENSP00000471265.1

Frequencies

GnomAD3 genomes AF: 0.245 AC: 35132 AN: 143624 Hom.: 7605 Cov.: 31

Gnomad AFR AF: 0.580

Gnomad AMI AF: 0.100

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.0793

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.0896

Gnomad MID AF: 0.159

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.198

GnomAD3 exomes AF: 0.124 AC: 2680 AN: 21662 Hom.: 461 AF XY: 0.125 AC XY: 1440 AN XY: 11542

Gnomad AFR exome AF: 0.605

Gnomad AMR exome AF: 0.0511

Gnomad ASJ exome AF: 0.0711

Gnomad EAS exome AF: 0.0387

Gnomad SAS exome AF: 0.167

Gnomad FIN exome AF: 0.0526

Gnomad NFE exome AF: 0.0779

Gnomad OTH exome AF: 0.0838

GnomAD4 exome AF: 0.128 AC: 17228 AN: 134336 Hom.: 1637 Cov.: 2 AF XY: 0.137 AC XY: 10241 AN XY: 74906

Gnomad4 AFR exome AF: 0.599

Gnomad4 AMR exome AF: 0.0674

Gnomad4 ASJ exome AF: 0.112

Gnomad4 EAS exome AF: 0.0841

Gnomad4 SAS exome AF: 0.182

Gnomad4 FIN exome AF: 0.0902

Gnomad4 NFE exome AF: 0.101

Gnomad4 OTH exome AF: 0.121

GnomAD4 genome AF: 0.245 AC: 35193 AN: 143770 Hom.: 7626 Cov.: 31 AF XY: 0.241 AC XY: 16834 AN XY: 69776

Gnomad4 AFR AF: 0.580

Gnomad4 AMR AF: 0.115

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.0784

Gnomad4 SAS AF: 0.215

Gnomad4 FIN AF: 0.0896

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.201

Alfa AF: 0.122 Hom.: 2619

Bravo AF: 0.249

Asia WGS AF: 0.157 AC: 546 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.74
DANN	Benign	0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3170368; hg19: chr19-3976321;