8-143580183-G-A

Variant names:

• chr8-143580183-G-A
• rs1062391
• NM_001130053.5:c.1734C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BA1

The NM_001130053.5(EEF1D):​c.1734C>T​(p.Ala578Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 1,612,984 control chromosomes in the GnomAD database, including 275,017 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.46 (19151 hom., cov: 32)
  • Exomes 𝑓: 0.58 (255866 hom.)
• Consequence: EEF1D NM_001130053.5 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.711

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]

ENSG00000279605 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.021).
• BP6: Variant 8-143580183-G-A is Benign according to our data. Variant chr8-143580183-G-A is described in ClinVar as [Benign]. Clinvar id is 3060516.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.711 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EEF1D	NM_001130053.5	c.1734C>T	p.Ala578Ala	synonymous_variant	Exon 9 of 10	ENST00000618139.4	NP_001123525.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EEF1D	ENST00000618139.4	c.1734C>T	p.Ala578Ala	synonymous_variant	Exon 9 of 10	5	NM_001130053.5	ENSP00000484536.2

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70355 AN: 151894 Hom.: 19147 Cov.: 32

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.578

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.622

Gnomad OTH AF: 0.490

GnomAD2 exomes AF: 0.510 AC: 127296 AN: 249582 AF XY: 0.518

Gnomad AFR exome AF: 0.152

Gnomad AMR exome AF: 0.432

Gnomad ASJ exome AF: 0.492

Gnomad EAS exome AF: 0.366

Gnomad FIN exome AF: 0.546

Gnomad NFE exome AF: 0.621

Gnomad OTH exome AF: 0.534

GnomAD4 exome AF: 0.583 AC: 851458 AN: 1460972 Hom.: 255866 Cov.: 67 AF XY: 0.580 AC XY: 421432 AN XY: 726764

Gnomad4 AFR exome AF: 0.149 AC: 4975 AN: 33468

Gnomad4 AMR exome AF: 0.444 AC: 19803 AN: 44642

Gnomad4 ASJ exome AF: 0.497 AC: 12992 AN: 26120

Gnomad4 EAS exome AF: 0.369 AC: 14651 AN: 39690

Gnomad4 SAS exome AF: 0.441 AC: 38024 AN: 86232

Gnomad4 FIN exome AF: 0.545 AC: 28902 AN: 52988

Gnomad4 NFE exome AF: 0.626 AC: 696324 AN: 1111748

Gnomad4 Remaining exome AF: 0.547 AC: 33012 AN: 60354

GnomAD4 genome AF: 0.463 AC: 70386 AN: 152012 Hom.: 19151 Cov.: 32 AF XY: 0.459 AC XY: 34100 AN XY: 74326

Gnomad4 AFR AF: 0.169 AC: 0.169118 AN: 0.169118

Gnomad4 AMR AF: 0.517 AC: 0.517422 AN: 0.517422

Gnomad4 ASJ AF: 0.505 AC: 0.50519 AN: 0.50519

Gnomad4 EAS AF: 0.374 AC: 0.373739 AN: 0.373739

Gnomad4 SAS AF: 0.430 AC: 0.429876 AN: 0.429876

Gnomad4 FIN AF: 0.544 AC: 0.544009 AN: 0.544009

Gnomad4 NFE AF: 0.622 AC: 0.622189 AN: 0.622189

Gnomad4 OTH AF: 0.494 AC: 0.493839 AN: 0.493839

Alfa AF: 0.560 Hom.: 84555

Bravo AF: 0.445

Asia WGS AF: 0.374 AC: 1304 AN: 3478

EpiCase AF: 0.624

EpiControl AF: 0.627

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

EEF1D-related disorder Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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_noAF	Benign	-0.54
CADD	Benign	14
DANN	Benign	0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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: rs1062391; hg19: chr8-144662353; COSMIC: COSV52782639; COSMIC: COSV52782639;