chr19-3976443-G-A

Position:

• chr19-3976443-G-A

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.*111C>T variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0202 in 1,289,062 control chromosomes in the GnomAD database, including 3,991 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.097 (2403 hom., cov: 33)
  • Exomes 𝑓: 0.0099 (1588 hom.)
• Consequence: EEF2 NM_001961.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.18

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=-0.77).
• BP6: Variant 19-3976443-G-A is Benign according to our data. Variant chr19-3976443-G-A is described in ClinVar as [Benign]. Clinvar id is 1280735.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EEF2	NM_001961.4	c.*111C>T		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	ENST00000309311.7	c.*111C>T		3_prime_UTR_variant	15/15	5	NM_001961.4	ENSP00000307940	P1
EEF2	ENST00000600794.1	c.108-143C>T		intron_variant		3		ENSP00000471265

Frequencies

GnomAD3 genomes AF: 0.0972 AC: 14777 AN: 152086 Hom.: 2397 Cov.: 33

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0381

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.00125

Gnomad OTH AF: 0.0641

GnomAD4 exome AF: 0.00985 AC: 11201 AN: 1136858 Hom.: 1588 Cov.: 16 AF XY: 0.00846 AC XY: 4792 AN XY: 566138

Gnomad4 AFR exome AF: 0.342

Gnomad4 AMR exome AF: 0.0207

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000936

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000651

Gnomad4 OTH exome AF: 0.0214

GnomAD4 genome AF: 0.0973 AC: 14813 AN: 152204 Hom.: 2403 Cov.: 33 AF XY: 0.0940 AC XY: 6995 AN XY: 74432

Gnomad4 AFR AF: 0.337

Gnomad4 AMR AF: 0.0380

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00125

Gnomad4 OTH AF: 0.0634

Alfa AF: 0.0946 Hom.: 247

Bravo AF: 0.113

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	May 11, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	17
DANN	Benign	0.89
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: rs2230567; hg19: chr19-3976441;