12-96199170-G-C

Variant names:

• chr12-96199170-G-C
• rs7959220
• NM_005230.4:c.-3+4465G>C

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+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
• Publications: 1 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.991 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+4465G>C		intron	N/A	NP_005221.2
	ELK3	NM_001413760.1		c.-117+4465G>C		intron	N/A	NP_001400689.1
	ELK3	NM_001413761.1		c.-3+1028G>C		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+4465G>C		intron	N/A	ENSP00000228741.3
	ELK3	ENST00000547860.1	TSL:3	c.-238+4465G>C		intron	N/A	ENSP00000447857.1
	ELK3	ENST00000552142.5	TSL:5	c.-3+4465G>C		intron	N/A	ENSP00000449430.1

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

African (AFR) AF: 0.999 AC: 41512 AN: 41552

American (AMR) AF: 0.997 AC: 15252 AN: 15294

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5177 AN: 5180

South Asian (SAS) AF: 0.998 AC: 4808 AN: 4820

European-Finnish (FIN) AF: 0.991 AC: 10524 AN: 10624

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 0.995 AC: 67674 AN: 68040

Other (OTH) AF: 1.00 AC: 2115 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	18
DANN	Benign	0.61
PhyloP100		0.84
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: rs7959220; hg19: chr12-96592948;