Variant chr1-205620271-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001973.4(ELK4):c.775C>T(p.Pro259Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,208 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Consequence

ELK4
NM_001973.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.33

Variant links:

Genes affected

ELK4 (HGNC:3326): (ETS transcription factor ELK4) This gene is a member of the Ets family of transcription factors and of the ternary complex factor (TCF) subfamily. Proteins of the TCF subfamily form a ternary complex by binding to the the serum response factor and the serum reponse element in the promoter of the c-fos proto-oncogene. The protein encoded by this gene is phosphorylated by the kinases, MAPK1 and MAPK8. Several transcript variants have been described for this gene. [provided by RefSeq, Jul 2008]

ELK4 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04716602).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELK4	NM_001973.4 linkuse as main transcript	c.775C>T	p.Pro259Ser	missense_variant	3/5	ENST00000357992.9	NP_001964.2	P28324-1A0A024R985Q8IXL1
ELK4	NM_021795.3 linkuse as main transcript	c.775C>T	p.Pro259Ser	missense_variant	3/3		NP_068567.1	P28324-2A0A024R997Q8IXL1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ELK4	ENST00000357992.9 linkuse as main transcript	c.775C>T	p.Pro259Ser	missense_variant	3/5	1	NM_001973.4	ENSP00000350681.4	P28324-1
ELK4	ENST00000289703.8 linkuse as main transcript	c.775C>T	p.Pro259Ser	missense_variant	3/3	1		ENSP00000289703.4	P28324-2
ELK4	ENST00000616704.4 linkuse as main transcript	n.775C>T		non_coding_transcript_exon_variant	3/10	2		ENSP00000483628.1	P28324-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

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:

0.0000302

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 27, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.75

CADD

Benign

8.0

DANN

Benign

0.17

DEOGEN2

Benign

0.24

T;.

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.055

LIST_S2

Benign

0.54

T;T

M_CAP

Benign

0.0056

MetaRNN

Benign

0.047

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.4

N;N

PROVEAN

Benign

0.39

N;N

REVEL

Benign

0.093

Sift

Benign

0.77

T;T

Sift4G

Benign

0.72

T;T

Polyphen

0.0

B;B

Vest4

0.036

MutPred

0.19

Loss of catalytic residue at P259 (P = 5e-04);Loss of catalytic residue at P259 (P = 5e-04);

MVP

0.42

MPC

0.15

ClinPred

0.017

GERP RS

0.049

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.016

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

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