chr1-231399838-C-T

Variant names:

• chr1-231399838-C-T
• rs2486729
• NM_022051.3:c.891+21160G>A

Variant summary

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

The NM_022051.3(EGLN1):​c.891+21160G>A 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 151,850 control chromosomes in the GnomAD database, including 24,198 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 (24198 hom., cov: 31)
• Consequence: EGLN1 NM_022051.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.117

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]

ENSG00000287856 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGLN1	NM_022051.3	c.891+21160G>A		intron_variant	Intron 1 of 4	ENST00000366641.4	NP_071334.1
EGLN1	NM_001377260.1	c.891+21160G>A		intron_variant	Intron 1 of 3		NP_001364189.1
EGLN1	NM_001377261.1	c.891+21160G>A		intron_variant	Intron 1 of 3		NP_001364190.1
EGLN1	XM_024447734.2	c.891+21160G>A		intron_variant	Intron 1 of 2		XP_024303502.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGLN1	ENST00000366641.4	c.891+21160G>A		intron_variant	Intron 1 of 4	1	NM_022051.3	ENSP00000355601.3
ENSG00000287856	ENST00000662216.1	c.31-25739G>A		intron_variant	Intron 3 of 6			ENSP00000499467.1

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82753 AN: 151736 Hom.: 24192 Cov.: 31

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.542

Gnomad ASJ AF: 0.625

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.710

Gnomad MID AF: 0.637

Gnomad NFE AF: 0.652

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: 82780 AN: 151850 Hom.: 24198 Cov.: 31 AF XY: 0.550 AC XY: 40826 AN XY: 74184

Gnomad4 AFR AF: 0.315

Gnomad4 AMR AF: 0.542

Gnomad4 ASJ AF: 0.625

Gnomad4 EAS AF: 0.548

Gnomad4 SAS AF: 0.573

Gnomad4 FIN AF: 0.710

Gnomad4 NFE AF: 0.652

Gnomad4 OTH AF: 0.564

Alfa AF: 0.616 Hom.: 29828

Bravo AF: 0.523

Asia WGS AF: 0.557 AC: 1936 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.4
DANN	Benign	0.54

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: rs2486729; hg19: chr1-231535584;