chr7-100722057-CTT-C

Variant names:

• chr7-100722057-CTT-C
• rs111249118
• NM_000799.4:c.246+23_246+24delTT

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_000799.4(EPO):​c.246+23_246+24delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00597 in 1,335,650 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 0.000099 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0067 (1 hom.)
• Consequence: EPO NM_000799.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.928

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPO	NM_000799.4	c.246+23_246+24delTT		intron_variant	Intron 3 of 4	ENST00000252723.3	NP_000790.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPO	ENST00000252723.3	c.246+10_246+11delTT		intron_variant	Intron 3 of 4	1	NM_000799.4	ENSP00000252723.2

Frequencies

GnomAD3 genomes AF: 0.0000923 AC: 13 AN: 140870 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000517

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00135

Gnomad FIN AF: 0.000120

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000156

Gnomad OTH AF: 0.000526

GnomAD4 exome AF: 0.00666 AC: 7954 AN: 1194790 Hom.: 1 AF XY: 0.00673 AC XY: 4020 AN XY: 597080

Gnomad4 AFR exome AF: 0.00709

Gnomad4 AMR exome AF: 0.0104

Gnomad4 ASJ exome AF: 0.00825

Gnomad4 EAS exome AF: 0.00657

Gnomad4 SAS exome AF: 0.00817

Gnomad4 FIN exome AF: 0.00694

Gnomad4 NFE exome AF: 0.00638

Gnomad4 OTH exome AF: 0.00683

GnomAD4 genome AF: 0.0000994 AC: 14 AN: 140860 Hom.: 1 Cov.: 31 AF XY: 0.000176 AC XY: 12 AN XY: 68272

Gnomad4 AFR AF: 0.000103

Gnomad4 AMR AF: 0.000144

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00114

Gnomad4 FIN AF: 0.000120

Gnomad4 NFE AF: 0.0000156

Gnomad4 OTH AF: 0.000524

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: rs111249118; hg19: chr7-100319680;