Variant chrX-47637043-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000343894.8(ELK1):c.280G>A(p.Ala94Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0008 in 1,208,342 control chromosomes in the GnomAD database, including 3 homozygotes. There are 280 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0044 ( 1 hom., 130 hem., cov: 22)

Exomes 𝑓: 0.00044 ( 2 hom. 150 hem. )

Consequence

ELK1
ENST00000343894.8 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.06

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=0.0034042597).

BP6

Variant X-47637043-C-T is Benign according to our data. Variant chrX-47637043-C-T is described in ClinVar as [Benign]. Clinvar id is 714924.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 130 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ELK1	NM_001114123.3 linkuse as main transcript	c.1158G>A	p.Ala386=	synonymous_variant	6/7	ENST00000376983.8
ELK1	NM_001257168.1 linkuse as main transcript	c.280G>A	p.Ala94Thr	missense_variant	5/6
ELK1	NM_005229.4 linkuse as main transcript	c.1158G>A	p.Ala386=	synonymous_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELK1	ENST00000343894.8 linkuse as main transcript	c.280G>A	p.Ala94Thr	missense_variant	5/6	1			P19419-2
ELK1	ENST00000376983.8 linkuse as main transcript	c.1158G>A	p.Ala386=	synonymous_variant	6/7	1	NM_001114123.3	P1	P19419-1
ELK1	ENST00000247161.7 linkuse as main transcript	c.1158G>A	p.Ala386=	synonymous_variant	5/6	1		P1	P19419-1

Frequencies

GnomAD3 genomes

AF:

0.00438

AC:

487

AN:

111087

Hom.:

Cov.:

AF XY:

0.00387

AC XY:

129

AN XY:

33335

show subpopulations

Gnomad AFR

AF:

0.0152

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00162

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:

0.0000756

Gnomad OTH

AF:

0.00202

GnomAD3 exomes

AF:

0.00122

AC:

218

AN:

178934

Hom.:

AF XY:

0.000808

AC XY:

AN XY:

64362

show subpopulations

Gnomad AFR exome

AF:

0.0138

Gnomad AMR exome

AF:

0.000920

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:

0.0000753

Gnomad OTH exome

AF:

0.00226

GnomAD4 exome

AF:

0.000437

AC:

480

AN:

1097203

Hom.:

Cov.:

AF XY:

0.000414

AC XY:

150

AN XY:

362663

show subpopulations

Gnomad4 AFR exome

AF:

0.0125

Gnomad4 AMR exome

AF:

0.000910

Gnomad4 ASJ exome

AF:

0.0000516

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000371

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000582

Gnomad4 OTH exome

AF:

0.00137

GnomAD4 genome

AF:

0.00438

AC:

487

AN:

111139

Hom.:

Cov.:

AF XY:

0.00389

AC XY:

130

AN XY:

33397

show subpopulations

Gnomad4 AFR

AF:

0.0152

Gnomad4 AMR

AF:

0.00161

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000756

Gnomad4 OTH

AF:

0.00199

Alfa

AF:

0.000719

Hom.:

Bravo

AF:

0.00514

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0162

AC:

ESP6500EA

AF:

0.000446

AC:

ExAC

AF:

0.00138

AC:

167

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

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.81

DANN

Benign

0.90

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.36

MetaRNN

Benign

0.0034

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.86

D;D;D;D

PROVEAN

Benign

1.6

REVEL

Benign

0.096

Sift

Benign

0.53

Sift4G

Benign

0.50

Vest4

0.098

MVP

0.37

ClinPred

0.013

GERP RS

-6.0

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