rs2069919

Positions:

• chr2-127421977-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000312.4(PROC):​c.237+528G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 152,110 control chromosomes in the GnomAD database, including 7,614 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 0.31 (7614 hom., cov: 33)
• Consequence: PROC NM_000312.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PROC	NM_000312.4	c.237+528G>A		intron_variant		ENST00000234071.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PROC	ENST00000234071.8	c.237+528G>A		intron_variant		1	NM_000312.4	P1

Frequencies

GnomAD3 genomes AF: 0.309 AC: 47001 AN: 151992 Hom.: 7620 Cov.: 33

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.00443

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.317

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

GnomAD4 genome AF: 0.309 AC: 47007 AN: 152110 Hom.: 7614 Cov.: 33 AF XY: 0.302 AC XY: 22467 AN XY: 74366

Gnomad4 AFR AF: 0.343

Gnomad4 AMR AF: 0.239

Gnomad4 ASJ AF: 0.350

Gnomad4 EAS AF: 0.00444

Gnomad4 SAS AF: 0.293

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.329

Gnomad4 OTH AF: 0.314

Alfa AF: 0.322 Hom.: 1491

Bravo AF: 0.307

Asia WGS AF: 0.143 AC: 500 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	12
DANN	Benign	0.83

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: rs2069919; hg19: chr2-128179553;