Variant 7-100722528-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000799.4(EPO):c.247-136C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0787 in 351,634 control chromosomes in the GnomAD database, including 870 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.090 ( 152 hom., cov: 0)

Exomes 𝑓: 0.076 ( 718 hom. )

Consequence

EPO
NM_000799.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.542

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 7-100722528-C-T is Benign according to our data. Variant chr7-100722528-C-T is described in ClinVar as [Benign]. Clinvar id is 1250657.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPO	NM_000799.4 linkuse as main transcript	c.247-136C>T		intron_variant		ENST00000252723.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPO	ENST00000252723.3 linkuse as main transcript	c.247-136C>T		intron_variant		1	NM_000799.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0904

AC:

5554

AN:

61424

Hom.:

154

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0255

Gnomad AMI

AF:

0.164

Gnomad AMR

AF:

0.100

Gnomad ASJ

AF:

0.157

Gnomad EAS

AF:

0.0174

Gnomad SAS

AF:

0.178

Gnomad FIN

AF:

0.0874

Gnomad MID

AF:

0.273

Gnomad NFE

AF:

0.111

Gnomad OTH

AF:

0.138

GnomAD4 exome

AF:

0.0762

AC:

22121

AN:

290200

Hom.:

718

AF XY:

0.0823

AC XY:

12572

AN XY:

152788

show subpopulations

Gnomad4 AFR exome

AF:

0.0205

Gnomad4 AMR exome

AF:

0.0703

Gnomad4 ASJ exome

AF:

0.0947

Gnomad4 EAS exome

AF:

0.00430

Gnomad4 SAS exome

AF:

0.160

Gnomad4 FIN exome

AF:

0.0532

Gnomad4 NFE exome

AF:

0.0747

Gnomad4 OTH exome

AF:

0.0740

GnomAD4 genome

AF:

0.0903

AC:

5548

AN:

61434

Hom.:

152

Cov.:

AF XY:

0.0922

AC XY:

2782

AN XY:

30166

show subpopulations

Gnomad4 AFR

AF:

0.0255

Gnomad4 AMR

AF:

0.100

Gnomad4 ASJ

AF:

0.157

Gnomad4 EAS

AF:

0.0174

Gnomad4 SAS

AF:

0.178

Gnomad4 FIN

AF:

0.0874

Gnomad4 NFE

AF:

0.111

Gnomad4 OTH

AF:

0.137

Alfa

AF:

0.0964

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.093

DANN

Benign

0.15

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over