Variant X-130069380-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001421.4(ELF4):c.1107G>A(p.Ser369Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00711 in 1,210,819 control chromosomes in the GnomAD database, including 35 homozygotes. There are 2,827 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0055 ( 3 hom., 181 hem., cov: 24)

Exomes 𝑓: 0.0073 ( 32 hom. 2646 hem. )

Consequence

ELF4
NM_001421.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0870

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 -17 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004645109).

BP6

Variant X-130069380-C-T is Benign according to our data. Variant chrX-130069380-C-T is described in ClinVar as [Benign]. Clinvar id is 788344.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-130069380-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.087 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELF4	NM_001421.4 link	c.1107G>A	p.Ser369Ser	synonymous_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 link	c.1107G>A	p.Ser369Ser	synonymous_variant	8/9	1	NM_001421.4	ENSP00000311280.6		Q99607
ELF4	ENST00000335997.11 link	c.1107G>A	p.Ser369Ser	synonymous_variant	8/9	1		ENSP00000338608.7		Q99607

Frequencies

GnomAD3 genomes

AF:

0.00553

AC:

622

AN:

112540

Hom.:

Cov.:

AF XY:

0.00522

AC XY:

181

AN XY:

34702

show subpopulations

Gnomad AFR

AF:

0.00126

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00178

Gnomad ASJ

AF:

0.00678

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000727

Gnomad FIN

AF:

0.0139

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00848

Gnomad OTH

AF:

0.00465

GnomAD3 exomes

AF:

0.00588

AC:

1079

AN:

183429

Hom.:

AF XY:

0.00591

AC XY:

401

AN XY:

67863

show subpopulations

Gnomad AFR exome

AF:

0.00129

Gnomad AMR exome

AF:

0.00128

Gnomad ASJ exome

AF:

0.00588

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000419

Gnomad FIN exome

AF:

0.0133

Gnomad NFE exome

AF:

0.00898

Gnomad OTH exome

AF:

0.00596

GnomAD4 exome

AF:

0.00728

AC:

7991

AN:

1098229

Hom.:

Cov.:

AF XY:

0.00728

AC XY:

2646

AN XY:

363583

show subpopulations

Gnomad4 AFR exome

AF:

0.000833

Gnomad4 AMR exome

AF:

0.00156

Gnomad4 ASJ exome

AF:

0.00583

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000517

Gnomad4 FIN exome

AF:

0.0142

Gnomad4 NFE exome

AF:

0.00821

Gnomad4 OTH exome

AF:

0.00555

GnomAD4 genome

AF:

0.00552

AC:

621

AN:

112590

Hom.:

Cov.:

AF XY:

0.00521

AC XY:

181

AN XY:

34762

show subpopulations

Gnomad4 AFR

AF:

0.00125

Gnomad4 AMR

AF:

0.00177

Gnomad4 ASJ

AF:

0.00678

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000364

Gnomad4 FIN

AF:

0.0139

Gnomad4 NFE

AF:

0.00848

Gnomad4 OTH

AF:

0.00459

Alfa

AF:

0.00665

Hom.:

Bravo

AF:

0.00470

TwinsUK

AF:

0.00809

AC:

ALSPAC

AF:

0.00762

AC:

ESP6500AA

AF:

0.000522

AC:

ESP6500EA

AF:

0.00936

AC:

ExAC

AF:

0.00605

AC:

735

EpiCase

AF:

0.00971

EpiControl

AF:

0.00830

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.61

CADD

Benign

3.7

DANN

Benign

0.64

DEOGEN2

Benign

0.017

FATHMM_MKL

Benign

0.053

LIST_S2

Benign

0.43

MetaRNN

Benign

0.0046

Sift4G

Benign

0.69

Vest4

0.068

MVP

0.51

GERP RS

2.4

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