12-96199170-G-C

Variant summary

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

The NM_005230.4(ELK3):c.-3+4465G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.996 in 152,304 control chromosomes in the GnomAD database, including 75,588 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 1.0 (75588 hom., cov: 32)
• Consequence: ELK3 NM_005230.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.843

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.991 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELK3	NM_005230.4	c.-3+4465G>C		intron_variant		ENST00000228741.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELK3	ENST00000228741.8	c.-3+4465G>C		intron_variant		1	NM_005230.4	P1
ELK3	ENST00000547249.1	c.-3+1028G>C		intron_variant		2
ELK3	ENST00000547860.1	c.-238+4465G>C		intron_variant		3
ELK3	ENST00000552142.5	c.-3+4465G>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.996 AC: 151622 AN: 152186 Hom.: 75529 Cov.: 32

Gnomad AFR AF: 0.999

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.997

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.998

Gnomad FIN AF: 0.991

Gnomad MID AF: 1.00

Gnomad NFE AF: 0.995

Gnomad OTH AF: 1.00

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

GnomAD4 genome AF: 0.996 AC: 151740 AN: 152304 Hom.: 75588 Cov.: 32 AF XY: 0.996 AC XY: 74163 AN XY: 74470

Gnomad4 AFR AF: 0.999

Gnomad4 AMR AF: 0.997

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.998

Gnomad4 FIN AF: 0.991

Gnomad4 NFE AF: 0.995

Gnomad4 OTH AF: 1.00

Alfa AF: 0.0763 Hom.: 184

Bravo AF: 0.997

Asia WGS AF: 1.00 AC: 3477 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	18
Dann	Benign	0.61

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: rs7959220; hg19: chr12-96592948;