rs2075362

Positions:

• chr12-96213111-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005230.4(ELK3):​c.-2-10454G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 151,998 control chromosomes in the GnomAD database, including 7,081 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.30 (7081 hom., cov: 32)
• Consequence: ELK3 NM_005230.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.454

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELK3	NM_005230.4	c.-2-10454G>A		intron_variant		ENST00000228741.8	NP_005221.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELK3	ENST00000228741.8	c.-2-10454G>A		intron_variant		1	NM_005230.4	ENSP00000228741	P1
ELK3	ENST00000547249.1	c.-2-10454G>A		intron_variant		2		ENSP00000446806
ELK3	ENST00000547860.1	c.-121+270G>A		intron_variant		3		ENSP00000447857
ELK3	ENST00000552142.5	c.-2-10454G>A		intron_variant		5		ENSP00000449430

Frequencies

GnomAD3 genomes AF: 0.296 AC: 44887 AN: 151880 Hom.: 7073 Cov.: 32

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.611

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.320

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.295 AC: 44915 AN: 151998 Hom.: 7081 Cov.: 32 AF XY: 0.296 AC XY: 21999 AN XY: 74306

Gnomad4 AFR AF: 0.303

Gnomad4 AMR AF: 0.347

Gnomad4 ASJ AF: 0.179

Gnomad4 EAS AF: 0.611

Gnomad4 SAS AF: 0.270

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.270

Gnomad4 OTH AF: 0.320

Alfa AF: 0.278 Hom.: 12340

Bravo AF: 0.311

Asia WGS AF: 0.416 AC: 1448 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.2
DANN	Benign	0.79

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

Other links and lift over

dbSNP: rs2075362; hg19: chr12-96606889;