1-231364368-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_022051.3(EGLN1):c.*2043C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00139 in 152,302 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EGLN1 NM_022051.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.242

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]

LOC107985360 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 1-231364368-G-A is Benign according to our data. Variant chr1-231364368-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 296149.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 213 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGLN1	NM_022051.3	c.*2043C>T		3_prime_UTR_variant	5/5	ENST00000366641.4
LOC107985360	XR_001738520.3	n.4098+2981G>A		intron_variant, non_coding_transcript_variant
EGLN1	NM_001377260.1	c.*2104C>T		3_prime_UTR_variant	4/4
EGLN1	NM_001377261.1	c.*2149C>T		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGLN1	ENST00000366641.4	c.*2043C>T		3_prime_UTR_variant	5/5	1	NM_022051.3	P1
EGLN1	ENST00000667629.1	c.*2149C>T		3_prime_UTR_variant	4/4

Frequencies

GnomAD3 genomes AF: 0.00140 AC: 213 AN: 152184 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000566

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00254

Gnomad OTH AF: 0.000959

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 16 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 14

Gnomad4 EAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.00139 AC: 212 AN: 152302 Hom.: 1 Cov.: 33 AF XY: 0.00120 AC XY: 89 AN XY: 74464

Gnomad4 AFR AF: 0.000241

Gnomad4 AMR AF: 0.00144

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000566

Gnomad4 NFE AF: 0.00253

Gnomad4 OTH AF: 0.000949

Alfa AF: 0.00206 Hom.: 0

Bravo AF: 0.00136

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Erythrocytosis, familial, 3 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	2.2
Dann	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs193073371; hg19: chr1-231500114;