dbSNP rs541569859: EGLN1:c.*1803dupA (chr1-231364607-A-AT) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_022051.3(EGLN1):c.*1803dupA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.57 ( 25910 hom., cov: 0)

Exomes 𝑓: 0.50 ( 0 hom. )

Consequence

EGLN1
NM_022051.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.160

Publications

2 publications found

Variant links:

Genes affected

EGLN1 (HGNC:1232): (egl-9 family hypoxia inducible factor 1) The protein encoded by this gene catalyzes the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. HIF is a transcriptional complex that plays a central role in mammalian oxygen homeostasis. This protein functions as a cellular oxygen sensor, and under normal oxygen concentration, modification by prolyl hydroxylation is a key regulatory event that targets HIF subunits for proteasomal destruction via the von Hippel-Lindau ubiquitylation complex. Mutations in this gene are associated with erythrocytosis familial type 3 (ECYT3). [provided by RefSeq, Nov 2009]

EGLN1 Gene-Disease associations (from GenCC):

erythrocytosis, familial, 3
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
autosomal dominant secondary polycythemia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hemoglobin, high altitude adaptation
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
hereditary pheochromocytoma-paraganglioma
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

EGLN1 links:

ENSG00000287856 (HGNC:):

ENSG00000287856 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022051.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EGLN1	NM_022051.3	MANE Select	c.*1803dupA	3_prime_UTR	Exon 5 of 5	NP_071334.1	R4SCQ0
EGLN1	NM_001377260.1		c.*1864dupA	3_prime_UTR	Exon 4 of 4	NP_001364189.1
EGLN1	NM_001377261.1		c.*1909dupA	3_prime_UTR	Exon 4 of 4	NP_001364190.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EGLN1	ENST00000366641.4	TSL:1 MANE Select	c.*1803dupA	3_prime_UTR	Exon 5 of 5	ENSP00000355601.3	Q9GZT9-1
EGLN1	ENST00000889867.1		c.*1803dupA	3_prime_UTR	Exon 6 of 6	ENSP00000559926.1
EGLN1	ENST00000889866.1		c.*1803dupA	3_prime_UTR	Exon 4 of 4	ENSP00000559925.1

Frequencies

GnomAD3 genomes

AF:

0.574

AC:

87197

AN:

151850

Hom.:

25902

Cov.:

show subpopulations

Gnomad AFR

AF:

0.410

Gnomad AMI

AF:

0.681

Gnomad AMR

AF:

0.553

Gnomad ASJ

AF:

0.629

Gnomad EAS

AF:

0.560

Gnomad SAS

AF:

0.578

Gnomad FIN

AF:

0.710

Gnomad MID

AF:

0.652

Gnomad NFE

AF:

0.654

Gnomad OTH

AF:

0.591

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.574

AC:

87238

AN:

151966

Hom.:

25910

Cov.:

AF XY:

0.578

AC XY:

42944

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.409

AC:

16939

AN:

41390

American (AMR)

AF:

0.553

AC:

8451

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.629

AC:

2182

AN:

3470

East Asian (EAS)

AF:

0.560

AC:

2901

AN:

5178

South Asian (SAS)

AF:

0.580

AC:

2798

AN:

4826

European-Finnish (FIN)

AF:

0.710

AC:

7496

AN:

10552

Middle Eastern (MID)

AF:

0.656

AC:

193

AN:

294

European-Non Finnish (NFE)

AF:

0.654

AC:

44422

AN:

67966

Other (OTH)

AF:

0.589

AC:

1240

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1829

3658

5486

7315

9144

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

740

1480

2220

2960

3700

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.502

Hom.:

1516

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.16

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over