Menu
GeneBe

12-96247566-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_005230.4(ELK3):c.834G>A(p.Ser278=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00148 in 1,613,896 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0071 ( 13 hom., cov: 32)
Exomes 𝑓: 0.00090 ( 11 hom. )

Consequence

ELK3
NM_005230.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0520
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 12-96247566-G-A is Benign according to our data. Variant chr12-96247566-G-A is described in ClinVar as [Benign]. Clinvar id is 778645.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.052 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0071 (1080/152062) while in subpopulation AFR AF= 0.024 (997/41462). AF 95% confidence interval is 0.0228. There are 13 homozygotes in gnomad4. There are 512 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 13 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ELK3NM_005230.4 linkuse as main transcriptc.834G>A p.Ser278= synonymous_variant 3/5 ENST00000228741.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ELK3ENST00000228741.8 linkuse as main transcriptc.834G>A p.Ser278= synonymous_variant 3/51 NM_005230.4 P1
ELK3ENST00000552142.5 linkuse as main transcriptc.208-12165G>A intron_variant 5
ELK3ENST00000549985.1 linkuse as main transcriptc.154-37G>A intron_variant, NMD_transcript_variant 3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00709
AC:
1078
AN:
151944
Hom.:
13
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00354
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.000221
Gnomad OTH
AF:
0.00527
GnomAD3 exomes
AF:
0.00203
AC:
510
AN:
251378
Hom.:
5
AF XY:
0.00142
AC XY:
193
AN XY:
135878
show subpopulations
Gnomad AFR exome
AF:
0.0260
Gnomad AMR exome
AF:
0.00150
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000463
Gnomad NFE exome
AF:
0.000246
Gnomad OTH exome
AF:
0.00114
GnomAD4 exome
AF:
0.000897
AC:
1311
AN:
1461834
Hom.:
11
Cov.:
32
AF XY:
0.000725
AC XY:
527
AN XY:
727218
show subpopulations
Gnomad4 AFR exome
AF:
0.0280
Gnomad4 AMR exome
AF:
0.00188
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000464
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.000151
Gnomad4 OTH exome
AF:
0.00176
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00710
AC:
1080
AN:
152062
Hom.:
13
Cov.:
32
AF XY:
0.00689
AC XY:
512
AN XY:
74308
show subpopulations
Gnomad4 AFR
AF:
0.0240
Gnomad4 AMR
AF:
0.00353
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000221
Gnomad4 OTH
AF:
0.00521
Alfa
AF:
0.00391
Hom.:
1
Bravo
AF:
0.00861
Asia WGS
AF:
0.00173
AC:
6
AN:
3478
EpiCase
AF:
0.000164
EpiControl
AF:
0.000237

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 submitterclinical testingInvitaeJul 11, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.51
Cadd
Benign
11
Dann
Benign
0.66
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs115218295; hg19: chr12-96641344; API