rs7542797

Variant names:

• chr1-231418041-A-C
• rs7542797
• NM_022051.3:c.891+2957T>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.891+2957T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,208 control chromosomes in the GnomAD database, including 1,965 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 0.16 (1965 hom., cov: 32)
• Consequence: EGLN1 NM_022051.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.60
• Publications: 7 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.173 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.891+2957T>G		intron	N/A	NP_071334.1	R4SCQ0
	EGLN1	NM_001377260.1		c.891+2957T>G		intron	N/A	NP_001364189.1
	EGLN1	NM_001377261.1		c.891+2957T>G		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.891+2957T>G		intron	N/A	ENSP00000355601.3	Q9GZT9-1
	ENSG00000287856	ENST00000662216.1		c.31-43942T>G		intron	N/A	ENSP00000499467.1	A0A590UJK7
	EGLN1	ENST00000476717.2	TSL:1	n.168+2135T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24211 AN: 152090 Hom.: 1960 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.0659

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.169

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

GnomAD4 genome AF: 0.159 AC: 24244 AN: 152208 Hom.: 1965 Cov.: 32 AF XY: 0.155 AC XY: 11570 AN XY: 74418

African (AFR) AF: 0.153 AC: 6335 AN: 41526

American (AMR) AF: 0.147 AC: 2254 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 481 AN: 3466

East Asian (EAS) AF: 0.112 AC: 579 AN: 5188

South Asian (SAS) AF: 0.143 AC: 691 AN: 4830

European-Finnish (FIN) AF: 0.144 AC: 1526 AN: 10596

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.175 AC: 11921 AN: 67986

Other (OTH) AF: 0.169 AC: 357 AN: 2114

Alfa AF: 0.170 Hom.: 3908

Bravo AF: 0.160

Asia WGS AF: 0.125 AC: 435 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.6
DANN	Benign	0.70
PhyloP100		1.6
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: rs7542797; hg19: chr1-231553787;