rs12199241

Variant names:

• chr6-8086267-C-T
• rs12199241
• NM_004280.5:c.384+3919G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004280.5(EEF1E1):​c.384+3919G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,006 control chromosomes in the GnomAD database, including 3,306 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.19 (3306 hom., cov: 31)
• Consequence: EEF1E1 NM_004280.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 5 publications found

Genes affected

EEF1E1 (HGNC:3212): (eukaryotic translation elongation factor 1 epsilon 1) This gene encodes a multifunctional protein that localizes to both the cytoplasm and nucleus. In the cytoplasm, the encoded protein is an auxiliary component of the macromolecular aminoacyl-tRNA synthase complex. However, its mouse homolog has been shown to translocate to the nucleus in response to DNA damage, and it plays a positive role in ATM/ATR-mediated p53 activation. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the neighboring downstream MUTED (muted homolog) gene. An EEF1E1-related pseudogene has been identified on chromosome 2. [provided by RefSeq, Dec 2010]

EEF1E1-BLOC1S5 (HGNC:49187): (EEF1E1-BLOC1S5 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring EEF1E1 (eukaryotic translation elongation factor 1 epsilon 1) and MUTED (muted homolog) genes on chromosome 6. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD) and is unlikely to produce a protein product. [provided by RefSeq, Dec 2010]

SCARNA27 (HGNC:33614): (small Cajal body-specific RNA 27)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EEF1E1	NM_004280.5	c.384+3919G>A		intron_variant	Intron 3 of 3	ENST00000379715.10	NP_004271.1
EEF1E1	NM_001135650.2	c.384+3919G>A		intron_variant	Intron 3 of 3		NP_001129122.1
EEF1E1-BLOC1S5	NR_037618.1	n.458+3919G>A		intron_variant	Intron 3 of 6
SCARNA27	NR_003703.1	n.*141G>A		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EEF1E1	ENST00000379715.10	c.384+3919G>A		intron_variant	Intron 3 of 3	1	NM_004280.5	ENSP00000369038.5
EEF1E1-BLOC1S5	ENST00000397456.2	n.384+3919G>A		intron_variant	Intron 3 of 6	3		ENSP00000380597.2
EEF1E1	ENST00000429723.6	c.384+3919G>A		intron_variant	Intron 3 of 3	3		ENSP00000414363.2
EEF1E1	ENST00000502429.5	c.342+3919G>A		intron_variant	Intron 3 of 3	3		ENSP00000427572.1

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29556 AN: 151888 Hom.: 3305 Cov.: 31

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.0883

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.193

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.194 AC: 29559 AN: 152006 Hom.: 3306 Cov.: 31 AF XY: 0.193 AC XY: 14346 AN XY: 74294

African (AFR) AF: 0.105 AC: 4353 AN: 41504

American (AMR) AF: 0.155 AC: 2366 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 509 AN: 3470

East Asian (EAS) AF: 0.0887 AC: 458 AN: 5164

South Asian (SAS) AF: 0.219 AC: 1055 AN: 4814

European-Finnish (FIN) AF: 0.254 AC: 2672 AN: 10534

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.258 AC: 17544 AN: 67916

Other (OTH) AF: 0.191 AC: 403 AN: 2108

Alfa AF: 0.227 Hom.: 6120

Bravo AF: 0.181

Asia WGS AF: 0.157 AC: 543 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.44
DANN	Benign	0.72
PhyloP100		-1.1
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

Other links and lift over

dbSNP: rs12199241; hg19: chr6-8086500;