Variant chr19-3980716-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001961.4(EEF2):c.1151-7C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00156 in 1,611,430 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0016 ( 1 hom. )

Consequence

EEF2
NM_001961.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00004264

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.559

Variant links:

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]

EEF2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 19-3980716-G-A is Benign according to our data. Variant chr19-3980716-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 447290.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 175 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EEF2	NM_001961.4 linkuse as main transcript	c.1151-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000309311.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EEF2	ENST00000309311.7 linkuse as main transcript	c.1151-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_001961.4	P1
EEF2	ENST00000598182.5 linkuse as main transcript	n.552C>T		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes

AF:

0.00115

AC:

175

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00210

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000984

AC:

246

AN:

249996

Hom.:

AF XY:

0.000983

AC XY:

133

AN XY:

135276

show subpopulations

Gnomad AFR exome

AF:

0.000309

Gnomad AMR exome

AF:

0.000842

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00179

Gnomad OTH exome

AF:

0.000820

GnomAD4 exome

AF:

0.00161

AC:

2346

AN:

1459206

Hom.:

Cov.:

AF XY:

0.00159

AC XY:

1154

AN XY:

725408

show subpopulations

Gnomad4 AFR exome

AF:

0.000300

Gnomad4 AMR exome

AF:

0.000830

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.00200

Gnomad4 OTH exome

AF:

0.00113

GnomAD4 genome

AF:

0.00115

AC:

175

AN:

152224

Hom.:

Cov.:

AF XY:

0.00102

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.000386

Gnomad4 AMR

AF:

0.000589

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00210

Gnomad4 OTH

AF:

0.00239

Alfa

AF:

0.00140

Hom.:

Bravo

AF:

0.00106

EpiCase

AF:

0.00142

EpiControl

AF:

0.00208

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Feb 01, 2021

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 21, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.035

DANN

Benign

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000043

dbscSNV1_RF

Benign

0.0080

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over