NM_022051.3:c.892-22467C>T

Variant names:

• chr1-231396566-G-A
• rs508618
• NM_022051.3:c.892-22467C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022051.3(EGLN1):​c.892-22467C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.804 in 152,104 control chromosomes in the GnomAD database, including 49,177 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.80 (49177 hom., cov: 31)
• Consequence: EGLN1 NM_022051.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45
• Publications: 14 publications found

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: Genomics England PanelApp, Ambry Genetics, 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

ENSG00000287856 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.842 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGLN1	NM_022051.3	MANE Select	c.892-22467C>T		intron	N/A	NP_071334.1
	EGLN1	NM_001377260.1		c.892-22467C>T		intron	N/A	NP_001364189.1
	EGLN1	NM_001377261.1		c.892-22467C>T		intron	N/A	NP_001364190.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGLN1	ENST00000366641.4	TSL:1 MANE Select	c.892-22467C>T		intron	N/A	ENSP00000355601.3
	ENSG00000287856	ENST00000662216.1		c.31-22467C>T		intron	N/A	ENSP00000499467.1
	EGLN1	ENST00000476717.2	TSL:1	n.169-22467C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.804 AC: 122178 AN: 151986 Hom.: 49142 Cov.: 31

Gnomad AFR AF: 0.803

Gnomad AMI AF: 0.889

Gnomad AMR AF: 0.738

Gnomad ASJ AF: 0.861

Gnomad EAS AF: 0.863

Gnomad SAS AF: 0.787

Gnomad FIN AF: 0.819

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.808

Gnomad OTH AF: 0.820

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.804 AC: 122265 AN: 152104 Hom.: 49177 Cov.: 31 AF XY: 0.805 AC XY: 59867 AN XY: 74350

African (AFR) AF: 0.803 AC: 33323 AN: 41476

American (AMR) AF: 0.738 AC: 11270 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.861 AC: 2988 AN: 3472

East Asian (EAS) AF: 0.863 AC: 4462 AN: 5172

South Asian (SAS) AF: 0.788 AC: 3795 AN: 4814

European-Finnish (FIN) AF: 0.819 AC: 8687 AN: 10604

Middle Eastern (MID) AF: 0.844 AC: 248 AN: 294

European-Non Finnish (NFE) AF: 0.808 AC: 54961 AN: 67988

Other (OTH) AF: 0.817 AC: 1720 AN: 2104

Alfa AF: 0.805 Hom.: 129243

Bravo AF: 0.799

Asia WGS AF: 0.817 AC: 2836 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.49
DANN	Benign	0.40
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs508618; hg19: chr1-231532312;