1-231399366-G-C

Variant names:

• chr1-231399366-G-C
• rs2749710
• NM_022051.3:c.891+21632C>G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2 BP4_Strong BS1

The NM_022051.3(EGLN1):​c.891+21632C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 152,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 32)
• Consequence: EGLN1 NM_022051.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0160

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 Likely_benign. Variant got -6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0000132 (2/152008) while in subpopulation EAS AF= 0.000386 (2/5182). AF 95% confidence interval is 0.0000683. There are 0 homozygotes in gnomad4. There are 2 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGLN1	NM_022051.3	c.891+21632C>G		intron_variant	Intron 1 of 4	ENST00000366641.4	NP_071334.1
EGLN1	NM_001377260.1	c.891+21632C>G		intron_variant	Intron 1 of 3		NP_001364189.1
EGLN1	NM_001377261.1	c.891+21632C>G		intron_variant	Intron 1 of 3		NP_001364190.1
EGLN1	XM_024447734.2	c.891+21632C>G		intron_variant	Intron 1 of 2		XP_024303502.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGLN1	ENST00000366641.4	c.891+21632C>G		intron_variant	Intron 1 of 4	1	NM_022051.3	ENSP00000355601.3
ENSG00000287856	ENST00000662216.1	c.31-25267C>G		intron_variant	Intron 3 of 6			ENSP00000499467.1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152008 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 152008 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74232

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	9.4
DANN	Benign	0.52

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: rs2749710; hg19: chr1-231535112;