rs1051475

Variant names:

• chr21-38823904-T-C
• rs1051475
• NM_005239.6:c.*1015T>C

Variant summary

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

The NM_005239.6(ETS2):​c.*1015T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 152,186 control chromosomes in the GnomAD database, including 8,800 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 0.34 (8774 hom., cov: 32)
  • Exomes 𝑓: 0.38 (26 hom.)
• Consequence: ETS2 NM_005239.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0940

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]

ENSG00000205622 (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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ETS2	NM_005239.6	c.*1015T>C		3_prime_UTR_variant	Exon 10 of 10	ENST00000360938.8	NP_005230.1
ETS2	NM_001256295.2	c.*1015T>C		3_prime_UTR_variant	Exon 11 of 11		NP_001243224.1
ETS2	XM_005260935.2	c.*1015T>C		3_prime_UTR_variant	Exon 10 of 10		XP_005260992.1
ETS2	XM_017028290.2	c.*1015T>C		3_prime_UTR_variant	Exon 10 of 10		XP_016883779.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ETS2	ENST00000360938.8	c.*1015T>C		3_prime_UTR_variant	Exon 10 of 10	1	NM_005239.6	ENSP00000354194.3

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51558 AN: 151682 Hom.: 8768 Cov.: 32

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.353

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.328

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.329

GnomAD4 exome AF: 0.376 AC: 145 AN: 386 Hom.: 26 Cov.: 0 AF XY: 0.397 AC XY: 89 AN XY: 224

Gnomad4 AFR exome AC: 0 AN: 0

Gnomad4 AMR exome AC: 0 AN: 0

Gnomad4 ASJ exome AC: 0 AN: 0

Gnomad4 EAS exome AC: 0 AN: 0

Gnomad4 SAS exome AC: 0 AN: 0

Gnomad4 FIN exome AF: 0.379 AC: 144 AN: 380

Gnomad4 NFE exome AF: 0.250 AC: 1 AN: 4

Gnomad4 Remaining exome AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.340 AC: 51596 AN: 151800 Hom.: 8774 Cov.: 32 AF XY: 0.339 AC XY: 25126 AN XY: 74176

Gnomad4 AFR AF: 0.314 AC: 0.313789 AN: 0.313789

Gnomad4 AMR AF: 0.346 AC: 0.346159 AN: 0.346159

Gnomad4 ASJ AF: 0.313 AC: 0.313149 AN: 0.313149

Gnomad4 EAS AF: 0.271 AC: 0.270898 AN: 0.270898

Gnomad4 SAS AF: 0.340 AC: 0.339975 AN: 0.339975

Gnomad4 FIN AF: 0.365 AC: 0.365381 AN: 0.365381

Gnomad4 NFE AF: 0.357 AC: 0.357303 AN: 0.357303

Gnomad4 OTH AF: 0.329 AC: 0.329373 AN: 0.329373

Alfa AF: 0.345 Hom.: 3574

Bravo AF: 0.334

Asia WGS AF: 0.304 AC: 1054 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	11
DANN	Benign	0.68
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

Publications

LitVar

Other links and lift over

dbSNP: rs1051475; hg19: chr21-40195828;