rs2075362

Variant names:

• chr12-96213111-G-A
• rs2075362
• NM_005230.4:c.-2-10454G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-96213111-G-A
• chr12-96213111-G-C
• chr12-96213111-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.-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
• Publications: 6 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.593 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.-2-10454G>A		intron	N/A	NP_005221.2
	ELK3	NM_001413760.1		c.-3+270G>A		intron	N/A	NP_001400689.1
	ELK3	NM_001413761.1		c.-2-10454G>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.-2-10454G>A		intron	N/A	ENSP00000228741.3
	ELK3	ENST00000547860.1	TSL:3	c.-121+270G>A		intron	N/A	ENSP00000447857.1
	ELK3	ENST00000552142.5	TSL:5	c.-2-10454G>A		intron	N/A	ENSP00000449430.1

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

African (AFR) AF: 0.303 AC: 12533 AN: 41426

American (AMR) AF: 0.347 AC: 5307 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 620 AN: 3468

East Asian (EAS) AF: 0.611 AC: 3160 AN: 5174

South Asian (SAS) AF: 0.270 AC: 1302 AN: 4818

European-Finnish (FIN) AF: 0.246 AC: 2597 AN: 10552

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.270 AC: 18369 AN: 67970

Other (OTH) AF: 0.320 AC: 676 AN: 2114

Alfa AF: 0.282 Hom.: 20004

Bravo AF: 0.311

Asia WGS AF: 0.416 AC: 1448 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.2
DANN	Benign	0.79
PhyloP100		-0.45
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: rs2075362; hg19: chr12-96606889;