Variant rs147839743 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_022051.3(EGLN1):c.1259C>T(p.Ser420Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000262 in 1,613,556 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00024 ( 1 hom. )

Consequence

EGLN1
NM_022051.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.59

Variant links:

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 links:

LOC107985360 (HGNC:):

LOC107985360 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006778419).

BP6

Variant 1-231366433-G-A is Benign according to our data. Variant chr1-231366433-G-A is described in ClinVar as [Benign]. Clinvar id is 465822.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 68 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
EGLN1	NM_022051.3 linkuse as main transcript	c.1259C>T	p.Ser420Leu	missense_variant	5/5	ENST00000366641.4	NP_071334.1
LOC107985360	XR_001738520.3 linkuse as main transcript	n.4099-3121G>A		intron_variant, non_coding_transcript_variant
EGLN1	NM_001377260.1 linkuse as main transcript	c.*39C>T		3_prime_UTR_variant	4/4		NP_001364189.1
EGLN1	NM_001377261.1 linkuse as main transcript	c.*84C>T		3_prime_UTR_variant	4/4		NP_001364190.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGLN1	ENST00000366641.4 linkuse as main transcript	c.1259C>T	p.Ser420Leu	missense_variant	5/5	1	NM_022051.3	ENSP00000355601	P1	Q9GZT9-1

Frequencies

GnomAD3 genomes

AF:

0.000448

AC:

AN:

151748

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00574

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.000660

AC:

166

AN:

251424

Hom.:

AF XY:

0.000648

AC XY:

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00707

Gnomad NFE exome

AF:

0.0000616

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000242

AC:

354

AN:

1461808

Hom.:

Cov.:

AF XY:

0.000227

AC XY:

165

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00590

Gnomad4 NFE exome

AF:

0.0000153

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.000448

AC:

AN:

151748

Hom.:

Cov.:

AF XY:

0.000648

AC XY:

AN XY:

74064

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00574

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000480

Alfa

AF:

0.0000278

Hom.:

Bravo

AF:

0.0000529

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000346

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Erythrocytosis, familial, 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 27, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.064

BayesDel_noAF

Benign

-0.090

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.84

M_CAP

Benign

0.029

MetaRNN

Benign

0.0068

MetaSVM

Uncertain

0.12

MutationAssessor

Benign

1.0

MutationTaster

Benign

0.89

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.6

REVEL

Uncertain

0.41

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.036

Polyphen

0.98

Vest4

0.32

MVP

0.47

MPC

1.1

ClinPred

0.030

GERP RS

5.8

Varity_R

0.094

gMVP

0.35

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over