Variant 12-96259757-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_005230.4(ELK3):c.1029G>A(p.Pro343=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0035 in 1,609,998 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0045 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0034 ( 26 hom. )

Consequence

ELK3
NM_005230.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.181

Variant links:

Genes affected

ELK3 (HGNC:3325): (ETS transcription factor ELK3) This gene encodes a member of the ETS-domain transcription factor family and the ternary complex factor (TCF) subfamily. Proteins in this subfamily regulate transcription when recruited by serum response factor to bind to serum response elements. This protein is activated by signal-induced phosphorylation; studies in rodents suggest that it is a transcriptional inhibitor in the absence of Ras, but activates transcription when Ras is present. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

ELK3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 12-96259757-G-A is Benign according to our data. Variant chr12-96259757-G-A is described in ClinVar as [Benign]. Clinvar id is 779607.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.181 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0034 (4950/1457744) while in subpopulation MID AF= 0.02 (115/5758). AF 95% confidence interval is 0.017. There are 26 homozygotes in gnomad4_exome. There are 2442 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELK3	NM_005230.4 linkuse as main transcript	c.1029G>A	p.Pro343=	synonymous_variant	4/5	ENST00000228741.8	NP_005221.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ELK3	ENST00000228741.8 linkuse as main transcript	c.1029G>A	p.Pro343=	synonymous_variant	4/5	1	NM_005230.4	ENSP00000228741	P1
ELK3	ENST00000552142.5 linkuse as main transcript	c.234G>A	p.Pro78=	synonymous_variant	3/4	5		ENSP00000449430
ELK3	ENST00000549529.1 linkuse as main transcript	n.118G>A		non_coding_transcript_exon_variant	2/3	2
ELK3	ENST00000549985.1 linkuse as main transcript	c.*5G>A		3_prime_UTR_variant, NMD_transcript_variant	3/4	3		ENSP00000449420

Frequencies

GnomAD3 genomes

AF:

0.00448

AC:

681

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00353

Gnomad AMI

AF:

0.0694

Gnomad AMR

AF:

0.00393

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00650

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00420

Gnomad OTH

AF:

0.00766

GnomAD3 exomes

AF:

0.00336

AC:

836

AN:

248620

Hom.:

AF XY:

0.00343

AC XY:

461

AN XY:

134498

show subpopulations

Gnomad AFR exome

AF:

0.00334

Gnomad AMR exome

AF:

0.00295

Gnomad ASJ exome

AF:

0.00556

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00169

Gnomad FIN exome

AF:

0.00659

Gnomad NFE exome

AF:

0.00357

Gnomad OTH exome

AF:

0.00563

GnomAD4 exome

AF:

0.00340

AC:

4950

AN:

1457744

Hom.:

Cov.:

AF XY:

0.00337

AC XY:

2442

AN XY:

725206

show subpopulations

Gnomad4 AFR exome

AF:

0.00410

Gnomad4 AMR exome

AF:

0.00303

Gnomad4 ASJ exome

AF:

0.00583

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00174

Gnomad4 FIN exome

AF:

0.00657

Gnomad4 NFE exome

AF:

0.00333

Gnomad4 OTH exome

AF:

0.00365

GnomAD4 genome

AF:

0.00447

AC:

680

AN:

152254

Hom.:

Cov.:

AF XY:

0.00424

AC XY:

316

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00351

Gnomad4 AMR

AF:

0.00393

Gnomad4 ASJ

AF:

0.00605

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.00650

Gnomad4 NFE

AF:

0.00420

Gnomad4 OTH

AF:

0.00758

Alfa

AF:

0.00382

Hom.:

Bravo

AF:

0.00421

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00312

EpiControl

AF:

0.00328

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	Jun 29, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

7.7

DANN

Benign

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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