chr7-100722057-C-CT

Variant names:

• chr7-100722057-C-CT
• rs111249118
• NM_000799.4:c.246+24dupT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000799.4(EPO):​c.246+24dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 1,297,310 control chromosomes in the GnomAD database, including 80 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.024 (79 hom., cov: 31)
  • Exomes 𝑓: 0.15 (1 hom.)
• Consequence: EPO NM_000799.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33

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 Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPO	NM_000799.4	c.246+24dupT		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+9_246+10insT		intron_variant	Intron 3 of 4	1	NM_000799.4	ENSP00000252723.2

Frequencies

GnomAD3 genomes AF: 0.0238 AC: 3345 AN: 140772 Hom.: 79 Cov.: 31

Gnomad AFR AF: 0.0631

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0125

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.00283

Gnomad SAS AF: 0.00564

Gnomad FIN AF: 0.0138

Gnomad MID AF: 0.00338

Gnomad NFE AF: 0.00820

Gnomad OTH AF: 0.0158

GnomAD4 exome AF: 0.150 AC: 173111 AN: 1156550 Hom.: 1 Cov.: 0 AF XY: 0.147 AC XY: 85112 AN XY: 577582

Gnomad4 AFR exome AF: 0.168

Gnomad4 AMR exome AF: 0.116

Gnomad4 ASJ exome AF: 0.130

Gnomad4 EAS exome AF: 0.117

Gnomad4 SAS exome AF: 0.146

Gnomad4 FIN exome AF: 0.0997

Gnomad4 NFE exome AF: 0.155

Gnomad4 OTH exome AF: 0.145

GnomAD4 genome AF: 0.0238 AC: 3350 AN: 140760 Hom.: 79 Cov.: 31 AF XY: 0.0227 AC XY: 1552 AN XY: 68224

Gnomad4 AFR AF: 0.0632

Gnomad4 AMR AF: 0.0125

Gnomad4 ASJ AF: 0.00634

Gnomad4 EAS AF: 0.00284

Gnomad4 SAS AF: 0.00568

Gnomad4 FIN AF: 0.0138

Gnomad4 NFE AF: 0.00820

Gnomad4 OTH AF: 0.0157

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;