1-231385732-C-T

Position:

• chr1-231385732-C-T

Variant summary

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

The NM_022051.3(EGLN1):​c.892-11633G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 152,136 control chromosomes in the GnomAD database, including 29,031 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 0.62 (29031 hom., cov: 33)
• Consequence: EGLN1 NM_022051.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35

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=-0.91).
• 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/exons	MANE	Protein	UniProt
EGLN1	NM_022051.3	c.892-11633G>A		intron_variant		ENST00000366641.4	NP_071334.1
EGLN1	NM_001377260.1	c.892-11633G>A		intron_variant			NP_001364189.1
EGLN1	NM_001377261.1	c.892-11633G>A		intron_variant			NP_001364190.1
EGLN1	XM_024447734.2	c.892-11633G>A		intron_variant			XP_024303502.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGLN1	ENST00000366641.4	c.892-11633G>A		intron_variant		1	NM_022051.3	ENSP00000355601.3
ENSG00000287856	ENST00000662216.1	c.31-11633G>A		intron_variant				ENSP00000499467.1

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93673 AN: 152018 Hom.: 29001 Cov.: 33

Gnomad AFR AF: 0.561

Gnomad AMI AF: 0.679

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.625

Gnomad EAS AF: 0.559

Gnomad SAS AF: 0.576

Gnomad FIN AF: 0.709

Gnomad MID AF: 0.643

Gnomad NFE AF: 0.652

Gnomad OTH AF: 0.614

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

GnomAD4 genome AF: 0.616 AC: 93750 AN: 152136 Hom.: 29031 Cov.: 33 AF XY: 0.619 AC XY: 46028 AN XY: 74372

Gnomad4 AFR AF: 0.561

Gnomad4 AMR AF: 0.568

Gnomad4 ASJ AF: 0.625

Gnomad4 EAS AF: 0.559

Gnomad4 SAS AF: 0.578

Gnomad4 FIN AF: 0.709

Gnomad4 NFE AF: 0.652

Gnomad4 OTH AF: 0.613

Alfa AF: 0.632 Hom.: 30743

Bravo AF: 0.603

Asia WGS AF: 0.582 AC: 2023 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.066
DANN	Benign	0.28

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: rs2486736; hg19: chr1-231521478; COSMIC: COSV64148452;