rs11687512

Positions:

• chr2-46322287-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001430.5(EPAS1):​c.26+24350G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0328 in 152,252 control chromosomes in the GnomAD database, including 139 homozygotes. 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 0.033 (139 hom., cov: 32)
• Consequence: EPAS1 NM_001430.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22

Genes affected

EPAS1 (HGNC:3374): (endothelial PAS domain protein 1) This gene encodes a transcription factor involved in the induction of genes regulated by oxygen, which is induced as oxygen levels fall. The encoded protein contains a basic-helix-loop-helix domain protein dimerization domain as well as a domain found in proteins in signal transduction pathways which respond to oxygen levels. Mutations in this gene are associated with erythrocytosis familial type 4. [provided by RefSeq, Nov 2009]

EPAS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0328 (4993/152252) while in subpopulation NFE AF= 0.0475 (3231/68020). AF 95% confidence interval is 0.0461. There are 139 homozygotes in gnomad4. There are 2560 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 4993 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPAS1	NM_001430.5	c.26+24350G>C		intron_variant		ENST00000263734.5	NP_001421.2
EPAS1	XM_011532698.3	c.-3525G>C		5_prime_UTR_variant	1/16		XP_011531000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPAS1	ENST00000263734.5	c.26+24350G>C		intron_variant		1	NM_001430.5	ENSP00000263734.3
EPAS1	ENST00000449347.5	c.26+24350G>C		intron_variant		3		ENSP00000406137.1
EPAS1	ENST00000460015.1	n.433-24586G>C		intron_variant		4
EPAS1	ENST00000467888.5	n.174+24350G>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0328 AC: 4993 AN: 152134 Hom.: 139 Cov.: 32

Gnomad AFR AF: 0.00751

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0151

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0118

Gnomad FIN AF: 0.0981

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0475

Gnomad OTH AF: 0.0287

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

GnomAD4 genome AF: 0.0328 AC: 4993 AN: 152252 Hom.: 139 Cov.: 32 AF XY: 0.0344 AC XY: 2560 AN XY: 74440

Gnomad4 AFR AF: 0.00748

Gnomad4 AMR AF: 0.0150

Gnomad4 ASJ AF: 0.0104

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0118

Gnomad4 FIN AF: 0.0981

Gnomad4 NFE AF: 0.0475

Gnomad4 OTH AF: 0.0279

Alfa AF: 0.0434 Hom.: 25

Bravo AF: 0.0244

Asia WGS AF: 0.00577 AC: 20 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	16
DANN	Benign	0.75

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: rs11687512; hg19: chr2-46549426;