rs541569859

Variant names:

• chr1-231364607-A-AT
• rs541569859
• NM_022051.3:c.*1803dupA

Your query was ambiguous. Multiple possible variants found:

• chr1-231364607-A-AT
• chr1-231364607-A-ATT
• chr1-231364607-A-ATTTTTTTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_022051.3(EGLN1):​c.*1803dupA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.57 (25910 hom., cov: 0)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: EGLN1 NM_022051.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.160

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGLN1	NM_022051.3	c.*1803dupA		3_prime_UTR_variant	Exon 5 of 5	ENST00000366641.4	NP_071334.1
EGLN1	NM_001377260.1	c.*1864dupA		3_prime_UTR_variant	Exon 4 of 4		NP_001364189.1
EGLN1	NM_001377261.1	c.*1909dupA		3_prime_UTR_variant	Exon 4 of 4		NP_001364190.1
LOC107985360	XR_001738520.3	n.4098+3227dupT		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGLN1	ENST00000366641	c.*1803dupA		3_prime_UTR_variant	Exon 5 of 5	1	NM_022051.3	ENSP00000355601.3
EGLN1	ENST00000667629	c.*1909dupA		3_prime_UTR_variant	Exon 4 of 4			ENSP00000499629.1
ENSG00000287856	ENST00000653908	c.*1909dupA		3_prime_UTR_variant	Exon 5 of 5			ENSP00000499669.1
ENSG00000287856	ENST00000653198.1	n.2626dupA		non_coding_transcript_exon_variant	Exon 8 of 8

Frequencies

GnomAD3 genomes AF: 0.574 AC: 87197 AN: 151850 Hom.: 25902 Cov.: 0

Gnomad AFR AF: 0.410

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.629

Gnomad EAS AF: 0.560

Gnomad SAS AF: 0.578

Gnomad FIN AF: 0.710

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.654

Gnomad OTH AF: 0.591

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 FIN exome AF: 0.500

GnomAD4 genome AF: 0.574 AC: 87238 AN: 151966 Hom.: 25910 Cov.: 0 AF XY: 0.578 AC XY: 42944 AN XY: 74268

Gnomad4 AFR AF: 0.409

Gnomad4 AMR AF: 0.553

Gnomad4 ASJ AF: 0.629

Gnomad4 EAS AF: 0.560

Gnomad4 SAS AF: 0.580

Gnomad4 FIN AF: 0.710

Gnomad4 NFE AF: 0.654

Gnomad4 OTH AF: 0.589

Alfa AF: 0.502 Hom.: 1516

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs541569859; hg19: chr1-231500353;