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GeneBe

12-96259757-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.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

2

Clinical Significance

Benign criteria provided, single submitter B:1

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]

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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=-0.54).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 12-96259757-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_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=-0.181 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
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
?
    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 5 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ELK3NM_005230.4 linkuse as main transcriptc.1029G>A p.Pro343= synonymous_variant 4/5 ENST00000228741.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ELK3ENST00000228741.8 linkuse as main transcriptc.1029G>A p.Pro343= synonymous_variant 4/51 NM_005230.4 P1
ELK3ENST00000552142.5 linkuse as main transcriptc.234G>A p.Pro78= synonymous_variant 3/45
ELK3ENST00000549529.1 linkuse as main transcriptn.118G>A non_coding_transcript_exon_variant 2/32
ELK3ENST00000549985.1 linkuse as main transcriptc.*5G>A 3_prime_UTR_variant, NMD_transcript_variant 3/43

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00448
AC:
681
AN:
152136
Hom.:
5
Cov.:
33
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.:
3
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.:
26
Cov.:
32
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00447
AC:
680
AN:
152254
Hom.:
5
Cov.:
33
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.:
1
Bravo
AF:
0.00421
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.00312
EpiControl
AF:
0.00328

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 testingInvitaeJun 29, 2018- -

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.

Other links and lift over

dbSNP: rs144750378; hg19: chr12-96653535; API