chr3-128272684-A-G

Variant names:

• chr3-128272684-A-G
• rs2811415
• NM_021937.5:c.786+7903A>G

Variant summary

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

The NM_021937.5(EEFSEC):​c.786+7903A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.805 in 152,184 control chromosomes in the GnomAD database, including 49,686 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 0.81 (49686 hom., cov: 32)
• Consequence: EEFSEC NM_021937.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.393
• Publications: 19 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EEFSEC	NM_021937.5	c.786+7903A>G		intron_variant	Intron 4 of 6	ENST00000254730.11	NP_068756.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EEFSEC	ENST00000254730.11	c.786+7903A>G		intron_variant	Intron 4 of 6	1	NM_021937.5	ENSP00000254730.5
EEFSEC	ENST00000483457.1	c.621+10460A>G		intron_variant	Intron 3 of 4	5		ENSP00000417660.1
EEFSEC	ENST00000484438.1	n.364+25641A>G		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.805 AC: 122437 AN: 152066 Hom.: 49636 Cov.: 32

Gnomad AFR AF: 0.704

Gnomad AMI AF: 0.658

Gnomad AMR AF: 0.856

Gnomad ASJ AF: 0.813

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.805

Gnomad FIN AF: 0.845

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.836

Gnomad OTH AF: 0.815

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

GnomAD4 genome AF: 0.805 AC: 122542 AN: 152184 Hom.: 49686 Cov.: 32 AF XY: 0.807 AC XY: 60073 AN XY: 74424

African (AFR) AF: 0.704 AC: 29233 AN: 41498

American (AMR) AF: 0.857 AC: 13102 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.813 AC: 2821 AN: 3472

East Asian (EAS) AF: 0.994 AC: 5152 AN: 5182

South Asian (SAS) AF: 0.805 AC: 3878 AN: 4820

European-Finnish (FIN) AF: 0.845 AC: 8955 AN: 10600

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.836 AC: 56837 AN: 68006

Other (OTH) AF: 0.817 AC: 1724 AN: 2110

Alfa AF: 0.827 Hom.: 165371

Bravo AF: 0.805

Asia WGS AF: 0.897 AC: 3117 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.64
DANN	Benign	0.59
PhyloP100		-0.39
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: rs2811415; hg19: chr3-127991527; COSMIC: COSV54622964;