Variant chr7-100722598-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000799.4(EPO):c.247-66G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0712 in 1,404,506 control chromosomes in the GnomAD database, including 4,073 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.051 ( 306 hom., cov: 32)

Exomes 𝑓: 0.074 ( 3767 hom. )

Consequence

EPO
NM_000799.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.69

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 7-100722598-G-A is Benign according to our data. Variant chr7-100722598-G-A is described in ClinVar as [Benign]. Clinvar id is 1241878.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0756 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.247-66G>A		intron_variant		ENST00000252723.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPO	ENST00000252723.3 linkuse as main transcript	c.247-66G>A		intron_variant		1	NM_000799.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0515

AC:

7832

AN:

152162

Hom.:

307

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0148

Gnomad AMI

AF:

0.0351

Gnomad AMR

AF:

0.0374

Gnomad ASJ

AF:

0.122

Gnomad EAS

AF:

0.000773

Gnomad SAS

AF:

0.0621

Gnomad FIN

AF:

0.0439

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0774

Gnomad OTH

AF:

0.0589

GnomAD4 exome

AF:

0.0736

AC:

92121

AN:

1252226

Hom.:

3767

AF XY:

0.0738

AC XY:

45737

AN XY:

619846

show subpopulations

Gnomad4 AFR exome

AF:

0.0141

Gnomad4 AMR exome

AF:

0.0334

Gnomad4 ASJ exome

AF:

0.122

Gnomad4 EAS exome

AF:

0.000105

Gnomad4 SAS exome

AF:

0.0725

Gnomad4 FIN exome

AF:

0.0486

Gnomad4 NFE exome

AF:

0.0800

Gnomad4 OTH exome

AF:

0.0686

GnomAD4 genome

AF:

0.0514

AC:

7826

AN:

152280

Hom.:

306

Cov.:

AF XY:

0.0497

AC XY:

3701

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0148

Gnomad4 AMR

AF:

0.0374

Gnomad4 ASJ

AF:

0.122

Gnomad4 EAS

AF:

0.000775

Gnomad4 SAS

AF:

0.0617

Gnomad4 FIN

AF:

0.0439

Gnomad4 NFE

AF:

0.0774

Gnomad4 OTH

AF:

0.0582

Alfa

AF:

0.0604

Hom.:

Bravo

AF:

0.0499

Asia WGS

AF:

0.0230

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 11, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.86

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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