Variant rs2181440 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001421.4(ELF4):c.1509G>A(p.Thr503=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 1,207,984 control chromosomes in the GnomAD database, including 27,550 homozygotes. There are 100,244 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 2250 hom., 7342 hem., cov: 24)

Exomes 𝑓: 0.26 ( 25300 hom. 92902 hem. )

Consequence

ELF4
NM_001421.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -3.45

Variant links:

Genes affected

ELF4 (HGNC:3319): (E74 like ETS transcription factor 4) The protein encoded by this gene is a transcriptional activator that binds and activates the promoters of the CSF2, IL3, IL8, and PRF1 genes. The encoded protein is involved in natural killer cell development and function, innate immunity, and induction of cell cycle arrest in naive CD8+ cells. Two transcript variants encoding the same protein have been found for this gene.[provided by RefSeq, Jan 2010]

ELF4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant X-130067204-C-T is Benign according to our data. Variant chrX-130067204-C-T is described in ClinVar as [Benign]. Clinvar id is 402824.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-130067204-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-3.45 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELF4	NM_001421.4 linkuse as main transcript	c.1509G>A	p.Thr503=	synonymous_variant	9/9	ENST00000308167.10	NP_001412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELF4	ENST00000308167.10 linkuse as main transcript	c.1509G>A	p.Thr503=	synonymous_variant	9/9	1	NM_001421.4	ENSP00000311280	P1
ELF4	ENST00000335997.11 linkuse as main transcript	c.1509G>A	p.Thr503=	synonymous_variant	9/9	1		ENSP00000338608	P1

Frequencies

GnomAD3 genomes

AF:

0.215

AC:

24061

AN:

111875

Hom.:

2251

Cov.:

AF XY:

0.215

AC XY:

7339

AN XY:

34069

show subpopulations

Gnomad AFR

AF:

0.0709

Gnomad AMI

AF:

0.322

Gnomad AMR

AF:

0.365

Gnomad ASJ

AF:

0.278

Gnomad EAS

AF:

0.114

Gnomad SAS

AF:

0.238

Gnomad FIN

AF:

0.254

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.265

Gnomad OTH

AF:

0.245

GnomAD3 exomes

AF:

0.254

AC:

45328

AN:

178787

Hom.:

4260

AF XY:

0.249

AC XY:

16212

AN XY:

65007

show subpopulations

Gnomad AFR exome

AF:

0.0665

Gnomad AMR exome

AF:

0.363

Gnomad ASJ exome

AF:

0.278

Gnomad EAS exome

AF:

0.114

Gnomad SAS exome

AF:

0.251

Gnomad FIN exome

AF:

0.259

Gnomad NFE exome

AF:

0.266

Gnomad OTH exome

AF:

0.274

GnomAD4 exome

AF:

0.257

AC:

281919

AN:

1096059

Hom.:

25300

Cov.:

AF XY:

0.257

AC XY:

92902

AN XY:

361801

show subpopulations

Gnomad4 AFR exome

AF:

0.0671

Gnomad4 AMR exome

AF:

0.362

Gnomad4 ASJ exome

AF:

0.275

Gnomad4 EAS exome

AF:

0.133

Gnomad4 SAS exome

AF:

0.253

Gnomad4 FIN exome

AF:

0.262

Gnomad4 NFE exome

AF:

0.263

Gnomad4 OTH exome

AF:

0.259

GnomAD4 genome

AF:

0.215

AC:

24056

AN:

111925

Hom.:

2250

Cov.:

AF XY:

0.215

AC XY:

7342

AN XY:

34129

show subpopulations

Gnomad4 AFR

AF:

0.0708

Gnomad4 AMR

AF:

0.364

Gnomad4 ASJ

AF:

0.278

Gnomad4 EAS

AF:

0.114

Gnomad4 SAS

AF:

0.239

Gnomad4 FIN

AF:

0.254

Gnomad4 NFE

AF:

0.265

Gnomad4 OTH

AF:

0.242

Alfa

AF:

0.257

Hom.:

2428

Bravo

AF:

0.216

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jan 24, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 41% of patients studied by a panel of primary immunodeficiencies. Number of patients: 39. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.11

DANN

Benign

0.59

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