rs551238

Variant names:

• chr7-100723905-G-A
• rs551238
• NM_000799.4:c.*772G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-100723905-G-A
• chr7-100723905-G-C
• chr7-100723905-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000799.4(EPO):​c.*772G>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: EPO NM_000799.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.87
• Publications: 0 publications found

Genes affected

EPO (HGNC:3415): (erythropoietin) This gene encodes a secreted, glycosylated cytokine composed of four alpha helical bundles. The encoded protein is mainly synthesized in the kidney, secreted into the blood plasma, and binds to the erythropoietin receptor to promote red blood cell production, or erythropoiesis, in the bone marrow. Expression of this gene is upregulated under hypoxic conditions, in turn leading to increased erythropoiesis and enhanced oxygen-carrying capacity of the blood. Expression of this gene has also been observed in brain and in the eye, and elevated expression levels have been observed in diabetic retinopathy and ocular hypertension. Recombinant forms of the encoded protein exhibit neuroprotective activity against a variety of potential brain injuries, as well as antiapoptotic functions in several tissue types, and have been used in the treatment of anemia and to enhance the efficacy of cancer therapies. [provided by RefSeq, Aug 2017]

EPO Gene-Disease associations (from GenCC):

• erythrocytosis, familial, 5

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• autosomal dominant secondary polycythemia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Diamond-Blackfan anemia-like

  Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPO	NM_000799.4	c.*772G>A		downstream_gene_variant		ENST00000252723.3	NP_000790.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPO	ENST00000252723.3	c.*772G>A		downstream_gene_variant		1	NM_000799.4	ENSP00000252723.2

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	21
DANN	Benign	0.85
PhyloP100		1.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs551238; hg19: chr7-100321528;