Variant X-130069343-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001421.4(ELF4):c.1144G>A(p.Val382Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00019 in 1,210,842 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 87 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 9/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., 4 hem., cov: 24)

Exomes 𝑓: 0.00019 ( 0 hom. 83 hem. )

Consequence

ELF4
NM_001421.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:2

Conservation

PhyloP100: 1.18

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.052253664).

BP6

Variant X-130069343-C-T is Benign according to our data. Variant chrX-130069343-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1328021.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-130069343-C-T is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd4 at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELF4	NM_001421.4 linkuse as main transcript	c.1144G>A	p.Val382Ile	missense_variant	8/9	ENST00000308167.10	NP_001412.1	Q99607

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELF4	ENST00000308167.10 linkuse as main transcript	c.1144G>A	p.Val382Ile	missense_variant	8/9	1	NM_001421.4	ENSP00000311280.6		Q99607
ELF4	ENST00000335997.11 linkuse as main transcript	c.1144G>A	p.Val382Ile	missense_variant	8/9	1		ENSP00000338608.7		Q99607

Frequencies

GnomAD3 genomes

AF:

0.000169

AC:

AN:

112614

Hom.:

Cov.:

AF XY:

0.000115

AC XY:

AN XY:

34758

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000754

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000150

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000262

AC:

AN:

183464

Hom.:

AF XY:

0.000265

AC XY:

AN XY:

67898

show subpopulations

Gnomad AFR exome

AF:

0.000456

Gnomad AMR exome

AF:

0.000146

Gnomad ASJ exome

AF:

0.000267

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000629

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000244

Gnomad OTH exome

AF:

0.000882

GnomAD4 exome

AF:

0.000192

AC:

211

AN:

1098228

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

363584

show subpopulations

Gnomad4 AFR exome

AF:

0.000341

Gnomad4 AMR exome

AF:

0.000170

Gnomad4 ASJ exome

AF:

0.000258

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000757

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000135

Gnomad4 OTH exome

AF:

0.000347

GnomAD4 genome

AF:

0.000169

AC:

AN:

112614

Hom.:

Cov.:

AF XY:

0.000115

AC XY:

AN XY:

34758

show subpopulations

Gnomad4 AFR

AF:

0.000290

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000754

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000150

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000240

Hom.:

Bravo

AF:

0.000193

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000346

AC:

ESP6500AA

AF:

0.000522

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.000296

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.99

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.013

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.50

M_CAP

Benign

0.0033

MetaRNN

Benign

0.052

Sift4G

Benign

0.12

Vest4

0.020

MVP

0.67

ClinPred

0.12

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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