1-231364624-A-C

Variant names:

• chr1-231364624-A-C
• rs143135847
• NM_022051.3:c.*1787T>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_022051.3(EGLN1):​c.*1787T>G variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0106 in 152,316 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (27 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: EGLN1 NM_022051.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.09

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=-0.35).
• BP6: Variant 1-231364624-A-C is Benign according to our data. Variant chr1-231364624-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 296155.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0106 (1620/152316) while in subpopulation AFR AF= 0.0368 (1531/41590). AF 95% confidence interval is 0.0353. There are 27 homozygotes in gnomad4. There are 782 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1620 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGLN1	NM_022051.3	c.*1787T>G		3_prime_UTR_variant	Exon 5 of 5	ENST00000366641.4	NP_071334.1
EGLN1	NM_001377260.1	c.*1848T>G		3_prime_UTR_variant	Exon 4 of 4		NP_001364189.1
EGLN1	NM_001377261.1	c.*1893T>G		3_prime_UTR_variant	Exon 4 of 4		NP_001364190.1
LOC107985360	XR_001738520.3	n.4098+3237A>C		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGLN1	ENST00000366641	c.*1787T>G		3_prime_UTR_variant	Exon 5 of 5	1	NM_022051.3	ENSP00000355601.3
EGLN1	ENST00000667629	c.*1893T>G		3_prime_UTR_variant	Exon 4 of 4			ENSP00000499629.1
ENSG00000287856	ENST00000653908	c.*1893T>G		3_prime_UTR_variant	Exon 5 of 5			ENSP00000499669.1
ENSG00000287856	ENST00000653198.1	n.2610T>G		non_coding_transcript_exon_variant	Exon 8 of 8

Frequencies

GnomAD3 genomes AF: 0.0106 AC: 1614 AN: 152198 Hom.: 27 Cov.: 32

Gnomad AFR AF: 0.0368

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00574

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

GnomAD4 genome AF: 0.0106 AC: 1620 AN: 152316 Hom.: 27 Cov.: 32 AF XY: 0.0105 AC XY: 782 AN XY: 74476

Gnomad4 AFR AF: 0.0368

Gnomad4 AMR AF: 0.00458

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00615

Alfa AF: 0.00754 Hom.: 1

Bravo AF: 0.0120

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Erythrocytosis, familial, 3 Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	-0.35
CADD	Benign	14
DANN	Benign	0.87

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: rs143135847; hg19: chr1-231500370;