rs35508970

Variant names:

• chr2-46356142-C-CA
• rs35508970
• NM_001430.5:c.218-9_218-8insA

Your query was ambiguous. Multiple possible variants found:

• chr2-46356142-C-CA
• chr2-46356142-C-CGCTCT
• chr2-46356142-C-CT
• chr2-46356142-C-CTCT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001430.5(EPAS1):​c.218-9_218-8insA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000579 in 1,375,738 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000069 (0 hom., cov: 23)
  • Exomes 𝑓: 0.00065 (0 hom.)
• Consequence: EPAS1 NM_001430.5 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.628

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 795 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPAS1	NM_001430.5	c.218-9_218-8insA		splice_region_variant, intron_variant	Intron 2 of 15	ENST00000263734.5	NP_001421.2
EPAS1	XM_011532698.3	c.257-9_257-8insA		splice_region_variant, intron_variant	Intron 2 of 15		XP_011531000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPAS1	ENST00000263734.5	c.218-9_218-8insA		splice_region_variant, intron_variant	Intron 2 of 15	1	NM_001430.5	ENSP00000263734.3
EPAS1	ENST00000449347.5	c.218-9_218-8insA		splice_region_variant, intron_variant	Intron 3 of 6	3		ENSP00000406137.1
EPAS1	ENST00000463191.1	n.28_29insA		non_coding_transcript_exon_variant	Exon 1 of 4	2
EPAS1	ENST00000475822.1	n.409-9_409-8insA		splice_region_variant, intron_variant	Intron 2 of 2	4

Frequencies

GnomAD3 genomes AF: 0.00000690 AC: 1 AN: 144960 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000230

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000646 AC: 795 AN: 1230660 Hom.: 0 Cov.: 34 AF XY: 0.000611 AC XY: 378 AN XY: 618184

Gnomad4 AFR exome AF: 0.000995

Gnomad4 AMR exome AF: 0.000138

Gnomad4 ASJ exome AF: 0.000423

Gnomad4 EAS exome AF: 0.000102

Gnomad4 SAS exome AF: 0.000558

Gnomad4 FIN exome AF: 0.0000815

Gnomad4 NFE exome AF: 0.000737

Gnomad4 OTH exome AF: 0.000461

GnomAD4 genome AF: 0.00000689 AC: 1 AN: 145078 Hom.: 0 Cov.: 23 AF XY: 0.0000142 AC XY: 1 AN XY: 70318

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000230

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

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs35508970; hg19: chr2-46583281;