chr7-100722521-TCACTCAC-T

Position:

• chr7-100722521-TCACTCAC-T

Variant summary

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

The NM_000799.4(EPO):​c.247-142_247-136del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0062 in 635,788 control chromosomes in the GnomAD database, including 106 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.018 (76 hom., cov: 0)
  • Exomes 𝑓: 0.0023 (30 hom.)
• Consequence: EPO NM_000799.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.940

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 7-100722521-TCACTCAC-T is Benign according to our data. Variant chr7-100722521-TCACTCAC-T is described in ClinVar as [Benign]. Clinvar id is 1231689.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPO	NM_000799.4	c.247-142_247-136del		intron_variant		ENST00000252723.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPO	ENST00000252723.3	c.247-142_247-136del		intron_variant		1	NM_000799.4	P1

Frequencies

GnomAD3 genomes AF: 0.0184 AC: 2801 AN: 152136 Hom.: 75 Cov.: 0

Gnomad AFR AF: 0.0640

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.00812

GnomAD4 exome AF: 0.00234 AC: 1133 AN: 483534 Hom.: 30 AF XY: 0.00210 AC XY: 531 AN XY: 253102

Gnomad4 AFR exome AF: 0.0599

Gnomad4 AMR exome AF: 0.00454

Gnomad4 ASJ exome AF: 0.000145

Gnomad4 EAS exome AF: 0.0000320

Gnomad4 SAS exome AF: 0.000395

Gnomad4 FIN exome AF: 0.0000448

Gnomad4 NFE exome AF: 0.000373

Gnomad4 OTH exome AF: 0.00569

GnomAD4 genome AF: 0.0184 AC: 2806 AN: 152254 Hom.: 76 Cov.: 0 AF XY: 0.0172 AC XY: 1278 AN XY: 74458

Gnomad4 AFR AF: 0.0639

Gnomad4 AMR AF: 0.00654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000426

Gnomad4 OTH AF: 0.00851

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 29, 2021

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1562901711; hg19: chr7-100320144;