19-11377796-CA-CAA

Variant names:

• chr19-11377796-C-CA
• rs528356712
• NM_000121.4:c.*187dupT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_000121.4(EPOR):​c.*187dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000706 in 737,932 control chromosomes in the GnomAD database, including 2 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00073 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00070 (1 hom.)
• Consequence: EPOR NM_000121.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.786

Genes affected

EPOR (HGNC:3416): (erythropoietin receptor) This gene encodes the erythropoietin receptor which is a member of the cytokine receptor family. Upon erythropoietin binding, this receptor activates Jak2 tyrosine kinase which activates different intracellular pathways including: Ras/MAP kinase, phosphatidylinositol 3-kinase and STAT transcription factors. The stimulated erythropoietin receptor appears to have a role in erythroid cell survival. Defects in the erythropoietin receptor may produce erythroleukemia and familial erythrocytosis. Dysregulation of this gene may affect the growth of certain tumors. Alternate splicing results in multiple transcript variants.[provided by RefSeq, May 2010]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 110 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPOR	NM_000121.4	c.*187dupT		3_prime_UTR_variant	Exon 8 of 8	ENST00000222139.11	NP_000112.1
EPOR	NR_033663.2	n.2071dupT		non_coding_transcript_exon_variant	Exon 8 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPOR	ENST00000222139	c.*187dupT		3_prime_UTR_variant	Exon 8 of 8	1	NM_000121.4	ENSP00000222139.5

Frequencies

GnomAD3 genomes AF: 0.000730 AC: 110 AN: 150710 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00249

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000264

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000443

Gnomad OTH AF: 0.000484

GnomAD3 exomes AF: 0.000425 AC: 78 AN: 183728 Hom.: 0 AF XY: 0.000399 AC XY: 41 AN XY: 102708

Gnomad AFR exome AF: 0.00310

Gnomad AMR exome AF: 0.000409

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000447

Gnomad SAS exome AF: 0.000152

Gnomad FIN exome AF: 0.000206

Gnomad NFE exome AF: 0.000222

Gnomad OTH exome AF: 0.000805

GnomAD4 exome AF: 0.000700 AC: 411 AN: 587106 Hom.: 1 Cov.: 6 AF XY: 0.000663 AC XY: 213 AN XY: 321230

Gnomad4 AFR exome AF: 0.00291

Gnomad4 AMR exome AF: 0.000698

Gnomad4 ASJ exome AF: 0.000296

Gnomad4 EAS exome AF: 0.00102

Gnomad4 SAS exome AF: 0.000226

Gnomad4 FIN exome AF: 0.000824

Gnomad4 NFE exome AF: 0.000662

Gnomad4 OTH exome AF: 0.000833

GnomAD4 genome AF: 0.000729 AC: 110 AN: 150826 Hom.: 1 Cov.: 32 AF XY: 0.000788 AC XY: 58 AN XY: 73592

Gnomad4 AFR AF: 0.00248

Gnomad4 AMR AF: 0.000264

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000443

Gnomad4 OTH AF: 0.000479

Bravo AF: 0.000812

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs528356712; hg19: chr19-11488472;