1-231414422-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022051.3(EGLN1):c.891+6576T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 151,562 control chromosomes in the GnomAD database, including 19,249 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 0.48 (19249 hom., cov: 31)
• Consequence: EGLN1 NM_022051.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.820

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGLN1	NM_022051.3	c.891+6576T>C		intron_variant		ENST00000366641.4
EGLN1	NM_001377260.1	c.891+6576T>C		intron_variant
EGLN1	NM_001377261.1	c.891+6576T>C		intron_variant
EGLN1	XM_024447734.2	c.891+6576T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGLN1	ENST00000366641.4	c.891+6576T>C		intron_variant		1	NM_022051.3	P1

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72044 AN: 151444 Hom.: 19196 Cov.: 31

Gnomad AFR AF: 0.744

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.442

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.456

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

GnomAD4 genome AF: 0.476 AC: 72150 AN: 151562 Hom.: 19249 Cov.: 31 AF XY: 0.470 AC XY: 34812 AN XY: 74072

Gnomad4 AFR AF: 0.745

Gnomad4 AMR AF: 0.467

Gnomad4 ASJ AF: 0.390

Gnomad4 EAS AF: 0.442

Gnomad4 SAS AF: 0.435

Gnomad4 FIN AF: 0.284

Gnomad4 NFE AF: 0.357

Gnomad4 OTH AF: 0.457

Alfa AF: 0.373 Hom.: 11139

Bravo AF: 0.502

Asia WGS AF: 0.453 AC: 1579 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.19
Dann	Benign	0.48

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

LitVar

Other links and lift over

dbSNP: rs2808614; hg19: chr1-231550168;