7-100721598-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_000799.4(EPO):​c.54G>A​(p.Ser18Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000442 in 1,613,878 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0023 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00025 ( 4 hom. )

Consequence

EPO
NM_000799.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.04
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
Variant 7-100721598-G-A is Benign according to our data. Variant chr7-100721598-G-A is described in ClinVar as [Benign]. Clinvar id is 716882.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=1.04 with no splicing effect.
BS2
High Homozygotes in GnomAdExome4 at 4 AD,AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EPONM_000799.4 linkc.54G>A p.Ser18Ser synonymous_variant Exon 2 of 5 ENST00000252723.3 NP_000790.2 P01588G9JKG7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EPOENST00000252723.3 linkc.54G>A p.Ser18Ser synonymous_variant Exon 2 of 5 1 NM_000799.4 ENSP00000252723.2 P01588

Frequencies

GnomAD3 genomes
AF:
0.00229
AC:
348
AN:
152136
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00801
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00239
GnomAD3 exomes
AF:
0.000630
AC:
158
AN:
250728
Hom.:
1
AF XY:
0.000450
AC XY:
61
AN XY:
135556
show subpopulations
Gnomad AFR exome
AF:
0.00825
Gnomad AMR exome
AF:
0.000405
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.000196
Gnomad FIN exome
AF:
0.0000465
Gnomad NFE exome
AF:
0.00000883
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000251
AC:
367
AN:
1461624
Hom.:
4
Cov.:
31
AF XY:
0.000216
AC XY:
157
AN XY:
727142
show subpopulations
Gnomad4 AFR exome
AF:
0.00935
Gnomad4 AMR exome
AF:
0.000313
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000139
Gnomad4 FIN exome
AF:
0.0000376
Gnomad4 NFE exome
AF:
0.00000809
Gnomad4 OTH exome
AF:
0.000282
GnomAD4 genome
AF:
0.00227
AC:
346
AN:
152254
Hom.:
1
Cov.:
32
AF XY:
0.00218
AC XY:
162
AN XY:
74434
show subpopulations
Gnomad4 AFR
AF:
0.00794
Gnomad4 AMR
AF:
0.000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00237
Alfa
AF:
0.00105
Hom.:
0
Bravo
AF:
0.00272
Asia WGS
AF:
0.000289
AC:
2
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

EPO-related disorder Benign:1
Apr 17, 2024
PreventionGenetics, part of Exact Sciences
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1
Dec 31, 2019
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.75
CADD
Benign
7.5
DANN
Benign
0.45
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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.

Other links and lift over

dbSNP: rs73409072; hg19: chr7-100319221; COSMIC: COSV99402722; API