Variant 1-231363991-CACAA-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_022051.3(EGLN1):c.*2416_*2419delTTGT variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.00173 in 152,198 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0017 ( 2 hom., cov: 33)

Failed GnomAD Quality Control

Consequence

EGLN1
NM_022051.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.79

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:

ENSG00000287856 (HGNC:):

ENSG00000287856 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 1-231363991-CACAA-C is Benign according to our data. Variant chr1-231363991-CACAA-C is described in ClinVar as [Likely_benign]. Clinvar id is 296144.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00173 (263/152198) while in subpopulation EAS AF= 0.0058 (30/5176). AF 95% confidence interval is 0.00472. There are 2 homozygotes in gnomad4. There are 125 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 263 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
EGLN1	NM_022051.3 link	c.2416_2419delTTGT	3_prime_UTR_variant	Exon 5 of 5	ENST00000366641.4	NP_071334.1	Q9GZT9-1R4SCQ0
EGLN1	NM_001377260.1 link	c.2477_2480delTTGT	3_prime_UTR_variant	Exon 4 of 4		NP_001364189.1
EGLN1	NM_001377261.1 link	c.2522_2525delTTGT	3_prime_UTR_variant	Exon 4 of 4		NP_001364190.1
LOC107985360	XR_001738520.3 link	n.4098+2608_4098+2611delAACA	intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
EGLN1	ENST00000366641 link	c.2416_2419delTTGT	3_prime_UTR_variant	Exon 5 of 5	1	NM_022051.3	ENSP00000355601.3	Q9GZT9-1
EGLN1	ENST00000667629 link	c.2522_2525delTTGT	3_prime_UTR_variant	Exon 4 of 4			ENSP00000499629.1	A0A590UJZ0
ENSG00000287856	ENST00000653908 link	c.2522_2525delTTGT	3_prime_UTR_variant	Exon 5 of 5			ENSP00000499669.1	A0A590UK27
ENSG00000287856	ENST00000653198.1 link	n.3239_3242delTTGT	non_coding_transcript_exon_variant	Exon 8 of 8

Frequencies

GnomAD3 genomes

AF:

0.00174

AC:

265

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00536

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00578

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00239

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

GnomAD4 genome

AF:

0.00173

AC:

263

AN:

152198

Hom.:

Cov.:

AF XY:

0.00168

AC XY:

125

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.00530

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00580

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00178

Hom.:

Bravo

AF:

0.00160

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Familial erythrocytosis

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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