chr12-96206002-G-A

Position:

• chr12-96206002-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.-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

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELK3	NM_005230.4	c.-3+11297G>A		intron_variant		ENST00000228741.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELK3	ENST00000228741.8	c.-3+11297G>A		intron_variant		1	NM_005230.4	P1
ELK3	ENST00000547249.1	c.-3+7860G>A		intron_variant		2
ELK3	ENST00000547860.1	c.-237-6723G>A		intron_variant		3
ELK3	ENST00000552142.5	c.-3+11297G>A		intron_variant		5

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

Gnomad4 AFR AF: 0.551

Gnomad4 AMR AF: 0.409

Gnomad4 ASJ AF: 0.682

Gnomad4 EAS AF: 0.202

Gnomad4 SAS AF: 0.631

Gnomad4 FIN AF: 0.512

Gnomad4 NFE AF: 0.552

Gnomad4 OTH AF: 0.520

Alfa AF: 0.549 Hom.: 43415

Bravo AF: 0.514

Asia WGS AF: 0.450 AC: 1565 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.5
DANN	Benign	0.60

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: rs2268509; hg19: chr12-96599780;