rs6753127

Variant names:

• chr2-46370157-T-C
• rs6753127
• NM_001430.5:c.886+224T>C

Your query was ambiguous. Multiple possible variants found:

• chr2-46370157-T-C
• chr2-46370157-T-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001430.5(EPAS1):​c.886+224T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.935 in 152,286 control chromosomes in the GnomAD database, including 66,572 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.93 (66572 hom., cov: 32)
• Consequence: EPAS1 NM_001430.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.27
• Publications: 7 publications found

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]

LINC01820 (HGNC:52625): (long intergenic non-protein coding RNA 1820)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 2-46370157-T-C is Benign according to our data. Variant chr2-46370157-T-C is described in ClinVar as Benign. ClinVar VariationId is 1292846.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001430.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPAS1	NM_001430.5	MANE Select	c.886+224T>C		intron	N/A	NP_001421.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPAS1	ENST00000263734.5	TSL:1 MANE Select	c.886+224T>C		intron	N/A	ENSP00000263734.3
	LINC01820	ENST00000843948.1		n.103-22098A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.935 AC: 142211 AN: 152168 Hom.: 66518 Cov.: 32

Gnomad AFR AF: 0.984

Gnomad AMI AF: 0.952

Gnomad AMR AF: 0.935

Gnomad ASJ AF: 0.931

Gnomad EAS AF: 0.916

Gnomad SAS AF: 0.895

Gnomad FIN AF: 0.885

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.916

Gnomad OTH AF: 0.935

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

GnomAD4 genome AF: 0.935 AC: 142321 AN: 152286 Hom.: 66572 Cov.: 32 AF XY: 0.933 AC XY: 69472 AN XY: 74458

African (AFR) AF: 0.984 AC: 40912 AN: 41576

American (AMR) AF: 0.934 AC: 14300 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.931 AC: 3231 AN: 3472

East Asian (EAS) AF: 0.916 AC: 4740 AN: 5176

South Asian (SAS) AF: 0.895 AC: 4316 AN: 4822

European-Finnish (FIN) AF: 0.885 AC: 9388 AN: 10602

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.916 AC: 62325 AN: 68016

Other (OTH) AF: 0.933 AC: 1972 AN: 2114

Alfa AF: 0.926 Hom.: 59300

Bravo AF: 0.942

Asia WGS AF: 0.895 AC: 3115 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.44
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6753127; hg19: chr2-46597296;