rs8128227

Variant names:

• chr21-38822370-C-A
• rs8128227
• NM_005239.6:c.1195-304C>A

Variant summary

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

The NM_005239.6(ETS2):​c.1195-304C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0453 in 152,294 control chromosomes in the GnomAD database, including 215 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 0.045 (215 hom., cov: 33)
• Consequence: ETS2 NM_005239.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.24
• Publications: 2 publications found

Genes affected

ETS2 (HGNC:3489): (ETS proto-oncogene 2, transcription factor) This gene encodes a transcription factor which regulates genes involved in development and apoptosis. The encoded protein is also a protooncogene and shown to be involved in regulation of telomerase. A pseudogene of this gene is located on the X chromosome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2012]

ETS2-AS1 (HGNC:56712): (ETS2 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0685 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005239.6. 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
	ETS2	NM_005239.6	MANE Select	c.1195-304C>A		intron	N/A	NP_005230.1
	ETS2	NM_001256295.2		c.1615-304C>A		intron	N/A	NP_001243224.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETS2	ENST00000360938.8	TSL:1 MANE Select	c.1195-304C>A		intron	N/A	ENSP00000354194.3
	ETS2	ENST00000667466.1		c.1300-304C>A		intron	N/A	ENSP00000499540.1
	ETS2	ENST00000360214.8	TSL:2	c.1195-304C>A		intron	N/A	ENSP00000353344.3

Frequencies

GnomAD3 genomes AF: 0.0453 AC: 6900 AN: 152176 Hom.: 215 Cov.: 33

Gnomad AFR AF: 0.0144

Gnomad AMI AF: 0.0769

Gnomad AMR AF: 0.0470

Gnomad ASJ AF: 0.0576

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0162

Gnomad FIN AF: 0.0322

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0701

Gnomad OTH AF: 0.0517

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

GnomAD4 genome AF: 0.0453 AC: 6899 AN: 152294 Hom.: 215 Cov.: 33 AF XY: 0.0431 AC XY: 3211 AN XY: 74476

African (AFR) AF: 0.0143 AC: 595 AN: 41562

American (AMR) AF: 0.0469 AC: 718 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0576 AC: 200 AN: 3472

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5172

South Asian (SAS) AF: 0.0160 AC: 77 AN: 4822

European-Finnish (FIN) AF: 0.0322 AC: 342 AN: 10624

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0702 AC: 4772 AN: 68018

Other (OTH) AF: 0.0511 AC: 108 AN: 2112

Alfa AF: 0.0381 Hom.: 35

Bravo AF: 0.0461

Asia WGS AF: 0.00837 AC: 30 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.0010
DANN	Benign	0.32
PhyloP100		-6.2
Mutation Taster		=100/0	polymorphism

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: rs8128227; hg19: chr21-40194294;