7-100722057-CT-C

Position:

• chr7-100722057-CT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000799.4(EPO):​c.246+24del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 1,216,430 control chromosomes in the GnomAD database, including 120 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.025 (115 hom., cov: 31)
  • Exomes 𝑓: 0.20 (5 hom.)
• Consequence: EPO NM_000799.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 7-100722057-CT-C is Benign according to our data. Variant chr7-100722057-CT-C is described in ClinVar as [Benign]. Clinvar id is 1271500.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPO	NM_000799.4	c.246+24del		intron_variant		ENST00000252723.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPO	ENST00000252723.3	c.246+24del		intron_variant		1	NM_000799.4	P1

Frequencies

GnomAD3 genomes AF: 0.0250 AC: 3511 AN: 140696 Hom.: 115 Cov.: 31

Gnomad AFR AF: 0.0767

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0169

Gnomad ASJ AF: 0.00151

Gnomad EAS AF: 0.00364

Gnomad SAS AF: 0.00226

Gnomad FIN AF: 0.00529

Gnomad MID AF: 0.0101

Gnomad NFE AF: 0.00301

Gnomad OTH AF: 0.0222

GnomAD4 exome AF: 0.202 AC: 216800 AN: 1075746 Hom.: 5 Cov.: 0 AF XY: 0.204 AC XY: 108767 AN XY: 534046

Gnomad4 AFR exome AF: 0.228

Gnomad4 AMR exome AF: 0.230

Gnomad4 ASJ exome AF: 0.222

Gnomad4 EAS exome AF: 0.238

Gnomad4 SAS exome AF: 0.201

Gnomad4 FIN exome AF: 0.217

Gnomad4 NFE exome AF: 0.197

Gnomad4 OTH exome AF: 0.213

GnomAD4 genome AF: 0.0250 AC: 3518 AN: 140684 Hom.: 115 Cov.: 31 AF XY: 0.0248 AC XY: 1688 AN XY: 68162

Gnomad4 AFR AF: 0.0768

Gnomad4 AMR AF: 0.0169

Gnomad4 ASJ AF: 0.00151

Gnomad4 EAS AF: 0.00345

Gnomad4 SAS AF: 0.00227

Gnomad4 FIN AF: 0.00529

Gnomad4 NFE AF: 0.00301

Gnomad4 OTH AF: 0.0221

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 27, 2021

- -

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;