rs4857841

Variant names:

• chr3-128327800-G-A
• rs4857841
• NM_021937.5:c.787-13433G>A

Variant summary

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

The NM_021937.5(EEFSEC):​c.787-13433G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 152,016 control chromosomes in the GnomAD database, including 16,392 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 0.43 (16392 hom., cov: 32)
• Consequence: EEFSEC NM_021937.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.806
• Publications: 28 publications found

Genes affected

EEFSEC (HGNC:24614): (eukaryotic elongation factor, selenocysteine-tRNA specific) Predicted to enable translation elongation factor activity. Predicted to be involved in selenocysteine incorporation. Predicted to be located in cytoplasm and nucleus. Predicted to be part of ribonucleoprotein complex. [provided by Alliance of Genome Resources, Apr 2022]

EEFSEC Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with progressive spasticity and brain abnormalities

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021937.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EEFSEC	NM_021937.5	MANE Select	c.787-13433G>A		intron	N/A	NP_068756.2
	EEFSEC	NM_001437809.1		c.787-13186G>A		intron	N/A	NP_001424738.1
	EEFSEC	NM_001437810.1		c.787-13433G>A		intron	N/A	NP_001424739.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EEFSEC	ENST00000254730.11	TSL:1 MANE Select	c.787-13433G>A		intron	N/A	ENSP00000254730.5
	EEFSEC	ENST00000483457.1	TSL:5	c.622-13433G>A		intron	N/A	ENSP00000417660.1
	EEFSEC	ENST00000484438.1	TSL:3	n.365-13433G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64613 AN: 151898 Hom.: 16368 Cov.: 32

Gnomad AFR AF: 0.708

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.385

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

GnomAD4 genome AF: 0.426 AC: 64683 AN: 152016 Hom.: 16392 Cov.: 32 AF XY: 0.427 AC XY: 31708 AN XY: 74306

African (AFR) AF: 0.708 AC: 29350 AN: 41450

American (AMR) AF: 0.429 AC: 6563 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 987 AN: 3460

East Asian (EAS) AF: 0.470 AC: 2422 AN: 5148

South Asian (SAS) AF: 0.454 AC: 2185 AN: 4808

European-Finnish (FIN) AF: 0.302 AC: 3194 AN: 10580

Middle Eastern (MID) AF: 0.353 AC: 103 AN: 292

European-Non Finnish (NFE) AF: 0.276 AC: 18760 AN: 67956

Other (OTH) AF: 0.384 AC: 811 AN: 2114

Alfa AF: 0.330 Hom.: 26141

Bravo AF: 0.441

Asia WGS AF: 0.451 AC: 1568 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.059
DANN	Benign	0.19
PhyloP100		-0.81
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: rs4857841; hg19: chr3-128046643;