rs1799809

Variant names:

• chr2-127418299-G-A
• rs1799809
• ENST00000883837.1:c.-137-1507G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-127418299-G-A
• chr2-127418299-G-C
• chr2-127418299-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000883837.1(PROC):​c.-137-1507G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 616,284 control chromosomes in the GnomAD database, including 106,407 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.52 (22574 hom., cov: 31)
  • Exomes 𝑓: 0.60 (83833 hom.)
• Consequence: PROC ENST00000883837.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0500
• Publications: 29 publications found

Genes affected

PROC (HGNC:9451): (protein C, inactivator of coagulation factors Va and VIIIa) This gene encodes a vitamin K-dependent plasma glycoprotein. The encoded protein is cleaved to its activated form by the thrombin-thrombomodulin complex. This activated form contains a serine protease domain and functions in degradation of the activated forms of coagulation factors V and VIII. Mutations in this gene have been associated with thrombophilia due to protein C deficiency, neonatal purpura fulminans, and recurrent venous thrombosis.[provided by RefSeq, Dec 2009]

PROC Gene-Disease associations (from GenCC):

• hereditary thrombophilia due to congenital protein C deficiency

  Inheritance: AD, SD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• thrombophilia due to protein C deficiency, autosomal dominant

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics
• thrombophilia due to protein C deficiency, autosomal recessive

  Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 2-127418299-G-A is Benign according to our data. Variant chr2-127418299-G-A is described in ClinVar as Benign. ClinVar VariationId is 1164170.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000883837.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PROC	NM_000312.4	MANE Select	c.-215G>A		upstream_gene	N/A	NP_000303.1	P04070-1
	PROC	NM_001375607.1		c.-148G>A		upstream_gene	N/A	NP_001362536.1
	PROC	NM_001375602.1		c.-148G>A		upstream_gene	N/A	NP_001362531.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PROC	ENST00000883837.1		c.-137-1507G>A		intron	N/A	ENSP00000553896.1
	PROC	ENST00000883838.1		c.-17-1627G>A		intron	N/A	ENSP00000553897.1
	PROC	ENST00000883839.1		c.-21-1623G>A		intron	N/A	ENSP00000553898.1

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79674 AN: 151916 Hom.: 22554 Cov.: 31

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.517

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.824

Gnomad SAS AF: 0.579

Gnomad FIN AF: 0.660

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.535

GnomAD4 exome AF: 0.596 AC: 276547 AN: 464248 Hom.: 83833 AF XY: 0.594 AC XY: 142355 AN XY: 239712

African (AFR) AF: 0.312 AC: 3626 AN: 11614

American (AMR) AF: 0.753 AC: 19556 AN: 25958

Ashkenazi Jewish (ASJ) AF: 0.521 AC: 4841 AN: 9292

East Asian (EAS) AF: 0.832 AC: 7933 AN: 9540

South Asian (SAS) AF: 0.570 AC: 32283 AN: 56654

European-Finnish (FIN) AF: 0.649 AC: 7254 AN: 11174

Middle Eastern (MID) AF: 0.507 AC: 1526 AN: 3012

European-Non Finnish (NFE) AF: 0.592 AC: 188362 AN: 318082

Other (OTH) AF: 0.590 AC: 11166 AN: 18922

GnomAD4 genome AF: 0.524 AC: 79727 AN: 152036 Hom.: 22574 Cov.: 31 AF XY: 0.534 AC XY: 39689 AN XY: 74308

African (AFR) AF: 0.312 AC: 12937 AN: 41456

American (AMR) AF: 0.659 AC: 10074 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.502 AC: 1741 AN: 3468

East Asian (EAS) AF: 0.824 AC: 4260 AN: 5168

South Asian (SAS) AF: 0.578 AC: 2783 AN: 4816

European-Finnish (FIN) AF: 0.660 AC: 6973 AN: 10566

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.577 AC: 39208 AN: 67972

Other (OTH) AF: 0.539 AC: 1138 AN: 2110

Alfa AF: 0.562 Hom.: 94825

Bravo AF: 0.518

Asia WGS AF: 0.719 AC: 2497 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Thrombophilia due to protein C deficiency, autosomal dominant (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	7.0
DANN	Benign	0.85
PhyloP100		0.050
PromoterAI		0.0090	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1799809;

hg19: chr2-128175875;