Variant X-130067217-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001421.4(ELF4):c.1496C>T(p.Pro499Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 1,210,194 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.000071 ( 0 hom., 0 hem., cov: 24)

Exomes 𝑓: 0.000023 ( 0 hom. 8 hem. )

Consequence

ELF4
NM_001421.4 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 1.24

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.051219344).

BS2

High Hemizygotes in GnomAdExome4 at 8 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELF4	NM_001421.4 linkuse as main transcript	c.1496C>T	p.Pro499Leu	missense_variant	9/9	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.1496C>T	p.Pro499Leu	missense_variant	9/9	1	NM_001421.4	ENSP00000311280.6		Q99607
ELF4	ENST00000335997.11 linkuse as main transcript	c.1496C>T	p.Pro499Leu	missense_variant	9/9	1		ENSP00000338608.7		Q99607

Frequencies

GnomAD3 genomes

AF:

0.0000710

AC:

AN:

112728

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34870

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000361

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000752

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000111

AC:

AN:

180513

Hom.:

AF XY:

0.0000150

AC XY:

AN XY:

66577

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000526

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000125

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000228

AC:

AN:

1097466

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

363018

show subpopulations

Gnomad4 AFR exome

AF:

0.0000758

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000662

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000190

Gnomad4 OTH exome

AF:

0.0000868

GnomAD4 genome

AF:

0.0000710

AC:

AN:

112728

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34870

show subpopulations

Gnomad4 AFR

AF:

0.0000966

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000361

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000752

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000756

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ELF4-related disorder

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 21, 2024

The ELF4 c.1496C>T variant is predicted to result in the amino acid substitution p.Pro499Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0055% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.94

CADD

Benign

DANN

Benign

0.78

DEOGEN2

Benign

0.099

T;T;T

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.70

.;T;T

M_CAP

Benign

0.0033

MetaRNN

Benign

0.051

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.46

N;N;.

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.70

N;N;.

REVEL

Benign

0.071

Sift

Benign

0.095

T;T;.

Sift4G

Benign

0.84

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.081

MVP

0.21

MPC

0.31

ClinPred

0.026

GERP RS

1.8

Varity_R

0.050

gMVP

0.38

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