chr8-143580571-C-A

Position:

chr8-143580571-C-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001130053.5(EEF1D):c.1645G>T(p.Ala549Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000167 in 1,613,390 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00096 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000084 ( 0 hom. )

Consequence

EEF1D
NM_001130053.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.78

Variant links:

Genes affected

EEF1D (HGNC:3211): (eukaryotic translation elongation factor 1 delta) This gene encodes a subunit of the elongation factor-1 complex, which is responsible for the enzymatic delivery of aminoacyl tRNAs to the ribosome. This subunit, delta, functions as guanine nucleotide exchange factor. It is reported that following HIV-1 infection, this subunit interacts with HIV-1 Tat. This interaction results in repression of translation of host cell proteins and enhanced translation of viral proteins. Several alternatively spliced transcript variants encoding multiple isoforms have been found for this gene. Related pseudogenes have been defined on chromosomes 1, 6, 7, 9, 11, 13, 17, 19.[provided by RefSeq, Aug 2010]

EEF1D links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.01365155).

BP6

Variant 8-143580571-C-A is Benign according to our data. Variant chr8-143580571-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 3049853.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EEF1D	NM_001130053.5 linkuse as main transcript	c.1645G>T	p.Ala549Ser	missense_variant	8/10	ENST00000618139.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	UniProt
EEF1D	ENST00000618139.4 linkuse as main transcript	c.1645G>T	p.Ala549Ser	missense_variant	8/10	5	NM_001130053.5	P29692-2
	ENST00000529247.1 linkuse as main transcript	n.332C>A		non_coding_transcript_exon_variant	2/2	3
	ENST00000623257.1 linkuse as main transcript	n.2214C>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.000966

AC:

147

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00340

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000243

AC:

AN:

250950

Hom.:

AF XY:

0.000184

AC XY:

AN XY:

135690

show subpopulations

Gnomad AFR exome

AF:

0.00333

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.0000835

AC:

122

AN:

1461024

Hom.:

Cov.:

AF XY:

0.0000592

AC XY:

AN XY:

726814

show subpopulations

Gnomad4 AFR exome

AF:

0.00293

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000265

GnomAD4 genome

AF:

0.000965

AC:

147

AN:

152366

Hom.:

Cov.:

AF XY:

0.000953

AC XY:

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.00339

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.0000591

Hom.:

Bravo

AF:

0.00115

ESP6500AA

AF:

0.00477

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000338

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

EEF1D-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 21, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.16

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.015

T;T;.;T;T;.;.;.;T;T;.;.;.;T;.;T;T;T

Eigen

Benign

0.17

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.92

D;.;D;D;D;D;.;.;.;.;D;D;D;D;D;.;D;D

M_CAP

Benign

0.016

MetaRNN

Benign

0.014

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.58

MutationAssessor

Uncertain

2.5

M;M;.;.;.;.;.;.;M;M;.;.;.;.;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D;D;D;D;D

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.9

N;N;N;N;N;N;N;N;N;N;N;N;.;N;N;N;N;N

REVEL

Benign

0.25

Sift

Benign

0.087

T;T;D;T;D;T;D;T;T;T;T;T;.;T;T;T;T;T

Sift4G

Benign

0.31

T;T;D;T;D;T;D;T;T;T;T;T;D;.;T;T;T;.

Polyphen

0.89

P;P;D;.;D;.;D;.;P;P;.;.;.;.;.;.;.;.

Vest4

0.36

MVP

0.78

MPC

0.22

ClinPred

0.065

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.30

gMVP

0.27

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

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