rs545937

Variant names:

• chr1-231407797-G-T
• rs545937
• NM_022051.3:c.891+13201C>A

Variant summary

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

The NM_022051.3(EGLN1):​c.891+13201C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 151,990 control chromosomes in the GnomAD database, including 2,069 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 0.15 (2069 hom., cov: 32)
• Consequence: EGLN1 NM_022051.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.283
• 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: 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.238 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.891+13201C>A		intron	N/A	NP_071334.1
	EGLN1	NM_001377260.1		c.891+13201C>A		intron	N/A	NP_001364189.1
	EGLN1	NM_001377261.1		c.891+13201C>A		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.891+13201C>A		intron	N/A	ENSP00000355601.3
	ENSG00000287856	ENST00000662216.1		c.31-33698C>A		intron	N/A	ENSP00000499467.1
	EGLN1	ENST00000476717.2	TSL:1	n.168+12379C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22629 AN: 151872 Hom.: 2065 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.0449

Gnomad SAS AF: 0.0749

Gnomad FIN AF: 0.0265

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.149 AC: 22656 AN: 151990 Hom.: 2069 Cov.: 32 AF XY: 0.142 AC XY: 10547 AN XY: 74296

African (AFR) AF: 0.242 AC: 10031 AN: 41424

American (AMR) AF: 0.132 AC: 2016 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 550 AN: 3466

East Asian (EAS) AF: 0.0453 AC: 232 AN: 5116

South Asian (SAS) AF: 0.0754 AC: 363 AN: 4816

European-Finnish (FIN) AF: 0.0265 AC: 280 AN: 10580

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8683 AN: 67996

Other (OTH) AF: 0.158 AC: 333 AN: 2112

Alfa AF: 0.134 Hom.: 757

Bravo AF: 0.162

Asia WGS AF: 0.0560 AC: 195 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.2
DANN	Benign	0.57
PhyloP100		-0.28
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: rs545937; hg19: chr1-231543543;