Variant X-130067487-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001421.4(ELF4):c.1226C>T(p.Ala409Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000089 in 112,341 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples 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 (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 23)

Consequence

ELF4
NM_001421.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.67

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.133522).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELF4	NM_001421.4 link	c.1226C>T	p.Ala409Val	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 link	c.1226C>T	p.Ala409Val	missense_variant	9/9	1	NM_001421.4	ENSP00000311280.6		Q99607
ELF4	ENST00000335997.11 link	c.1226C>T	p.Ala409Val	missense_variant	9/9	1		ENSP00000338608.7		Q99607

Frequencies

GnomAD3 genomes

AF:

0.00000890

AC:

AN:

112341

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34501

show subpopulations

Gnomad AFR

AF:

0.0000324

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000552

AC:

AN:

181310

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67036

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000125

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000890

AC:

AN:

112341

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34501

show subpopulations

Gnomad4 AFR

AF:

0.0000324

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000491

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 29, 2024

The c.1226C>T (p.A409V) alteration is located in exon 9 (coding exon 8) of the ELF4 gene. This alteration results from a C to T substitution at nucleotide position 1226, causing the alanine (A) at amino acid position 409 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.98

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

T;T

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.79

.;T

M_CAP

Benign

0.0046

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

L;L

PrimateAI

Benign

0.46

PROVEAN

Benign

0.040

N;N

REVEL

Benign

0.075

Sift

Benign

0.12

T;T

Sift4G

Benign

0.49

T;T

Polyphen

0.0080

B;B

Vest4

0.18

MutPred

0.31

Loss of sheet (P = 0.0011);Loss of sheet (P = 0.0011);

MVP

0.23

MPC

0.38

ClinPred

0.060

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.075

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