chr7-100723905-G-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_000799.4(EPO):​c.*772G>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 151,974 control chromosomes in the GnomAD database, including 29,481 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 0.62 (29481 hom., cov: 32)
• Consequence: EPO NM_000799.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.87
• Publications: 37 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.77 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPO	NM_000799.4	c.*772G>T		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>T		downstream_gene_variant		1	NM_000799.4	ENSP00000252723.2

Frequencies

GnomAD3 genomes AF: 0.621 AC: 94267 AN: 151856 Hom.: 29460 Cov.: 32

Gnomad AFR AF: 0.624

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.704

Gnomad ASJ AF: 0.713

Gnomad EAS AF: 0.790

Gnomad SAS AF: 0.643

Gnomad FIN AF: 0.526

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.596

Gnomad OTH AF: 0.666

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

GnomAD4 genome AF: 0.621 AC: 94334 AN: 151974 Hom.: 29481 Cov.: 32 AF XY: 0.624 AC XY: 46337 AN XY: 74238

African (AFR) AF: 0.624 AC: 25864 AN: 41462

American (AMR) AF: 0.704 AC: 10752 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.713 AC: 2474 AN: 3470

East Asian (EAS) AF: 0.790 AC: 4050 AN: 5124

South Asian (SAS) AF: 0.641 AC: 3089 AN: 4818

European-Finnish (FIN) AF: 0.526 AC: 5549 AN: 10558

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.596 AC: 40498 AN: 67962

Other (OTH) AF: 0.670 AC: 1412 AN: 2108

Alfa AF: 0.610 Hom.: 37558

Bravo AF: 0.634

Asia WGS AF: 0.697 AC: 2426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
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;