rs2024878

Variant names:

• chr1-231392669-C-A
• rs2024878
• NM_022051.3:c.892-18570G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-231392669-C-A
• chr1-231392669-C-G

Variant summary

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

The NM_022051.3(EGLN1):​c.892-18570G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 152,066 control chromosomes in the GnomAD database, including 24,231 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 0.55 (24231 hom., cov: 32)
• Consequence: EGLN1 NM_022051.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.419
• Publications: 6 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: 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

ENSG00000287856 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.646 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGLN1	NM_022051.3	MANE Select	c.892-18570G>T		intron	N/A	NP_071334.1	R4SCQ0
	EGLN1	NM_001377260.1		c.892-18570G>T		intron	N/A	NP_001364189.1
	EGLN1	NM_001377261.1		c.892-18570G>T		intron	N/A	NP_001364190.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGLN1	ENST00000366641.4	TSL:1 MANE Select	c.892-18570G>T		intron	N/A	ENSP00000355601.3	Q9GZT9-1
	ENSG00000287856	ENST00000662216.1		c.31-18570G>T		intron	N/A	ENSP00000499467.1	A0A590UJK7
	EGLN1	ENST00000476717.2	TSL:1	n.169-18570G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82896 AN: 151948 Hom.: 24225 Cov.: 32

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.679

Gnomad AMR AF: 0.542

Gnomad ASJ AF: 0.625

Gnomad EAS AF: 0.559

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.710

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.651

Gnomad OTH AF: 0.565

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

GnomAD4 genome AF: 0.545 AC: 82923 AN: 152066 Hom.: 24231 Cov.: 32 AF XY: 0.551 AC XY: 40922 AN XY: 74334

African (AFR) AF: 0.314 AC: 13020 AN: 41436

American (AMR) AF: 0.542 AC: 8282 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.625 AC: 2169 AN: 3470

East Asian (EAS) AF: 0.559 AC: 2885 AN: 5158

South Asian (SAS) AF: 0.573 AC: 2762 AN: 4822

European-Finnish (FIN) AF: 0.710 AC: 7520 AN: 10592

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.651 AC: 44288 AN: 67982

Other (OTH) AF: 0.563 AC: 1190 AN: 2114

Alfa AF: 0.582 Hom.: 4499

Bravo AF: 0.523

Asia WGS AF: 0.561 AC: 1950 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.4
DANN	Benign	0.53
PhyloP100		0.42
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: rs2024878; hg19: chr1-231528415; COSMIC: COSV64148548;