Variant chrX-47639035-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001114123.3(ELK1):c.514C>G(p.Pro172Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000801 in 1,202,537 control chromosomes in the GnomAD database, including 3 homozygotes. There are 277 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0046 ( 1 hom., 143 hem., cov: 23)

Exomes 𝑓: 0.00041 ( 2 hom. 134 hem. )

Consequence

ELK1
NM_001114123.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.72

Variant links:

Genes affected

ELK1 (HGNC:3321): (ETS transcription factor ELK1) 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 response element in the promoter of the c-fos proto-oncogene. The protein encoded by this gene is a nuclear target for the ras-raf-MAPK signaling cascade. This gene produces multiple isoforms by using alternative translational start codons and by alternative splicing. Related pseudogenes have been identified on chromosomes 7 and 14. [provided by RefSeq, Mar 2012]

ELK1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004161954).

BP6

Variant X-47639035-G-C is Benign according to our data. Variant chrX-47639035-G-C is described in ClinVar as [Benign]. Clinvar id is 714925.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 143 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ELK1	NM_001114123.3 linkuse as main transcript	c.514C>G	p.Pro172Ala	missense_variant	4/7	ENST00000376983.8
ELK1	NM_005229.4 linkuse as main transcript	c.514C>G	p.Pro172Ala	missense_variant	3/6
ELK1	NM_001257168.1 linkuse as main transcript	c.270+244C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELK1	ENST00000376983.8 linkuse as main transcript	c.514C>G	p.Pro172Ala	missense_variant	4/7	1	NM_001114123.3	P1	P19419-1
ELK1	ENST00000247161.7 linkuse as main transcript	c.514C>G	p.Pro172Ala	missense_variant	3/6	1		P1	P19419-1
ELK1	ENST00000343894.8 linkuse as main transcript	c.270+244C>G		intron_variant		1			P19419-2

Frequencies

GnomAD3 genomes

AF:

0.00458

AC:

517

AN:

112882

Hom.:

Cov.:

AF XY:

0.00406

AC XY:

142

AN XY:

35014

show subpopulations

Gnomad AFR

AF:

0.0158

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00176

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:

0.0000751

Gnomad OTH

AF:

0.00261

GnomAD3 exomes

AF:

0.00128

AC:

206

AN:

161064

Hom.:

AF XY:

0.000857

AC XY:

AN XY:

52538

show subpopulations

Gnomad AFR exome

AF:

0.0147

Gnomad AMR exome

AF:

0.00112

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:

0.0000284

Gnomad OTH exome

AF:

0.00247

GnomAD4 exome

AF:

0.000409

AC:

446

AN:

1089600

Hom.:

Cov.:

AF XY:

0.000375

AC XY:

134

AN XY:

357108

show subpopulations

Gnomad4 AFR exome

AF:

0.0128

Gnomad4 AMR exome

AF:

0.00107

Gnomad4 ASJ exome

AF:

0.0000524

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000381

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000131

Gnomad4 OTH exome

AF:

0.00125

GnomAD4 genome

AF:

0.00458

AC:

517

AN:

112937

Hom.:

Cov.:

AF XY:

0.00408

AC XY:

143

AN XY:

35079

show subpopulations

Gnomad4 AFR

AF:

0.0157

Gnomad4 AMR

AF:

0.00176

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000751

Gnomad4 OTH

AF:

0.00257

Alfa

AF:

0.00208

Hom.:

Bravo

AF:

0.00527

ESP6500AA

AF:

0.0157

AC:

ESP6500EA

AF:

0.000447

AC:

ExAC

AF:

0.00133

AC:

160

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 28, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.84

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.26

T;T

FATHMM_MKL

Uncertain

0.91

MetaRNN

Benign

0.0042

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.9

L;L

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.049

Sift

Benign

0.19

T;T

Sift4G

Benign

0.20

T;T

Polyphen

0.043

B;B

Vest4

0.23

MVP

0.43

MPC

0.88

ClinPred

0.022

GERP RS

2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.072

gMVP

0.34

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