chr2-127417267-T-C

Variant names:

• chr2-127417267-T-C
• rs2069901
• ENST00000883837.1:c.-138+870T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000883837.1(PROC):​c.-138+870T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 152,186 control chromosomes in the GnomAD database, including 16,016 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 0.44 (16016 hom., cov: 33)
• Consequence: PROC ENST00000883837.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.738
• Publications: 14 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):

• thrombophilia due to protein C deficiency, autosomal dominant

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

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

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.578 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PROC	ENST00000883837.1		c.-138+870T>C		intron	N/A	ENSP00000553896.1
	PROC	ENST00000883838.1		c.-18+870T>C		intron	N/A	ENSP00000553897.1
	PROC	ENST00000883839.1		c.-22+1132T>C		intron	N/A	ENSP00000553898.1

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67565 AN: 152068 Hom.: 15997 Cov.: 33

Gnomad AFR AF: 0.584

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.442

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

GnomAD4 genome AF: 0.444 AC: 67625 AN: 152186 Hom.: 16016 Cov.: 33 AF XY: 0.435 AC XY: 32353 AN XY: 74400

African (AFR) AF: 0.584 AC: 24260 AN: 41522

American (AMR) AF: 0.331 AC: 5060 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.494 AC: 1714 AN: 3472

East Asian (EAS) AF: 0.145 AC: 751 AN: 5176

South Asian (SAS) AF: 0.422 AC: 2039 AN: 4830

European-Finnish (FIN) AF: 0.338 AC: 3584 AN: 10588

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.422 AC: 28702 AN: 67992

Other (OTH) AF: 0.438 AC: 925 AN: 2114

Alfa AF: 0.488 Hom.: 4638

Bravo AF: 0.448

Asia WGS AF: 0.267 AC: 934 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.0
DANN	Benign	0.60
PhyloP100		-0.74

Splicing

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

Other links and lift over

dbSNP: rs2069901; hg19: chr2-128174843;