Variant 8-143580060-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001130053.5(EEF1D):c.1857G>A(p.Lys619=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0296 in 1,614,034 control chromosomes in the GnomAD database, including 882 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.022 ( 64 hom., cov: 33)

Exomes 𝑓: 0.030 ( 818 hom. )

Consequence

EEF1D
NM_001130053.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.895

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0058659315).

BP6

Variant 8-143580060-C-T is Benign according to our data. Variant chr8-143580060-C-T is described in ClinVar as [Benign]. Clinvar id is 3038338.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.895 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0221 (3372/152328) while in subpopulation NFE AF= 0.0349 (2375/68020). AF 95% confidence interval is 0.0337. There are 64 homozygotes in gnomad4. There are 1552 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 64 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EEF1D	NM_001130053.5 linkuse as main transcript	c.1857G>A	p.Lys619=	synonymous_variant	9/10	ENST00000618139.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	UniProt
EEF1D	ENST00000618139.4 linkuse as main transcript	c.1857G>A	p.Lys619=	synonymous_variant	9/10	5	NM_001130053.5	P29692-2
	ENST00000623257.1 linkuse as main transcript	n.1703C>T		non_coding_transcript_exon_variant	1/1
	ENST00000529247.1 linkuse as main transcript	n.268+157C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0222

AC:

3373

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00606

Gnomad AMI

AF:

0.0450

Gnomad AMR

AF:

0.0208

Gnomad ASJ

AF:

0.0326

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00621

Gnomad FIN

AF:

0.0175

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0349

Gnomad OTH

AF:

0.0258

GnomAD3 exomes

AF:

0.0231

AC:

5800

AN:

251256

Hom.:

103

AF XY:

0.0235

AC XY:

3196

AN XY:

135834

show subpopulations

Gnomad AFR exome

AF:

0.00486

Gnomad AMR exome

AF:

0.0137

Gnomad ASJ exome

AF:

0.0292

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00630

Gnomad FIN exome

AF:

0.0183

Gnomad NFE exome

AF:

0.0369

Gnomad OTH exome

AF:

0.0279

GnomAD4 exome

AF:

0.0304

AC:

44477

AN:

1461706

Hom.:

818

Cov.:

AF XY:

0.0298

AC XY:

21697

AN XY:

727166

show subpopulations

Gnomad4 AFR exome

AF:

0.00532

Gnomad4 AMR exome

AF:

0.0144

Gnomad4 ASJ exome

AF:

0.0326

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00667

Gnomad4 FIN exome

AF:

0.0186

Gnomad4 NFE exome

AF:

0.0355

Gnomad4 OTH exome

AF:

0.0268

GnomAD4 genome

AF:

0.0221

AC:

3372

AN:

152328

Hom.:

Cov.:

AF XY:

0.0208

AC XY:

1552

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00604

Gnomad4 AMR

AF:

0.0208

Gnomad4 ASJ

AF:

0.0326

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00600

Gnomad4 FIN

AF:

0.0175

Gnomad4 NFE

AF:

0.0349

Gnomad4 OTH

AF:

0.0255

Alfa

AF:

0.0312

Hom.:

Bravo

AF:

0.0223

TwinsUK

AF:

0.0302

AC:

112

ALSPAC

AF:

0.0345

AC:

133

ESP6500AA

AF:

0.00613

AC:

ESP6500EA

AF:

0.0350

AC:

301

ExAC

AF:

0.0243

AC:

2948

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

EEF1D-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 19, 2019

This variant is classified as 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

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.93

Eigen

Benign

0.11

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.33

MetaRNN

Benign

0.0059

MetaSVM

Benign

-0.97

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D;D;D;D;N

Sift4G

Pathogenic

0.0

Vest4

0.23

ClinPred

0.034

GERP RS

4.0

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