rs2268509

Variant names:

• chr12-96206002-G-A
• rs2268509
• NM_005230.4:c.-3+11297G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-96206002-G-A
• chr12-96206002-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005230.4(ELK3):​c.-3+11297G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 152,020 control chromosomes in the GnomAD database, including 21,921 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 0.53 (21921 hom., cov: 32)
• Consequence: ELK3 NM_005230.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.993
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005230.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELK3	NM_005230.4	MANE Select	c.-3+11297G>A		intron	N/A	NP_005221.2
	ELK3	NM_001413760.1		c.-116-6726G>A		intron	N/A	NP_001400689.1
	ELK3	NM_001413761.1		c.-3+7860G>A		intron	N/A	NP_001400690.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELK3	ENST00000228741.8	TSL:1 MANE Select	c.-3+11297G>A		intron	N/A	ENSP00000228741.3
	ELK3	ENST00000547860.1	TSL:3	c.-237-6723G>A		intron	N/A	ENSP00000447857.1
	ELK3	ENST00000552142.5	TSL:5	c.-3+11297G>A		intron	N/A	ENSP00000449430.1

Frequencies

GnomAD3 genomes AF: 0.528 AC: 80207 AN: 151902 Hom.: 21902 Cov.: 32

Gnomad AFR AF: 0.551

Gnomad AMI AF: 0.591

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.682

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.630

Gnomad FIN AF: 0.512

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.519

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

GnomAD4 genome AF: 0.528 AC: 80268 AN: 152020 Hom.: 21921 Cov.: 32 AF XY: 0.522 AC XY: 38802 AN XY: 74310

African (AFR) AF: 0.551 AC: 22844 AN: 41456

American (AMR) AF: 0.409 AC: 6240 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.682 AC: 2362 AN: 3464

East Asian (EAS) AF: 0.202 AC: 1045 AN: 5172

South Asian (SAS) AF: 0.631 AC: 3042 AN: 4824

European-Finnish (FIN) AF: 0.512 AC: 5397 AN: 10540

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.552 AC: 37514 AN: 67984

Other (OTH) AF: 0.520 AC: 1099 AN: 2112

Alfa AF: 0.543 Hom.: 93574

Bravo AF: 0.514

Asia WGS AF: 0.450 AC: 1565 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.5
DANN	Benign	0.60
PhyloP100		0.99
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2268509; hg19: chr12-96599780;