19-11377796-C-CAA

Variant summary

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

The NM_000121.4(EPOR):c.*187_*188insTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000987 in 739,942 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000086 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: EPOR NM_000121.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 GnomAd at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPOR	NM_000121.4	c.*187_*188insTT		3_prime_UTR_variant	8/8	ENST00000222139.11
EPOR	NR_033663.2	n.2071_2072insTT		non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPOR	ENST00000222139.11	c.*187_*188insTT		3_prime_UTR_variant	8/8	1	NM_000121.4	P1
EPOR	ENST00000588681.5	n.2099_2100insTT		non_coding_transcript_exon_variant	8/8	1
EPOR	ENST00000592375.6	c.*822_*823insTT		3_prime_UTR_variant	7/7	2

Frequencies

GnomAD3 genomes AF: 0.0000863 AC: 13 AN: 150710 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000660

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: 0.000177

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000120 AC: 22 AN: 183728 Hom.: 0 AF XY: 0.000136 AC XY: 14 AN XY: 102708

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000136

Gnomad ASJ exome AF: 0.000113

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000198

Gnomad OTH exome AF: 0.000201

GnomAD4 exome AF: 0.000102 AC: 60 AN: 589232 Hom.: 0 Cov.: 6 AF XY: 0.000109 AC XY: 35 AN XY: 322342

Gnomad4 AFR exome AF: 0.0000630

Gnomad4 AMR exome AF: 0.000168

Gnomad4 ASJ exome AF: 0.0000491

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000150

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000134

Gnomad4 OTH exome AF: 0.000128

GnomAD4 genome AF: 0.0000863 AC: 13 AN: 150710 Hom.: 0 Cov.: 32 AF XY: 0.0000953 AC XY: 7 AN XY: 73466

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000660

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000177

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Familial erythrocytosis Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Splicing

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;