rs2069910

chr2-127420398-T-Cchr2-127420398-T-G

Variant summary

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

The NM_000312.4(PROC):c.70+386T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 151,970 control chromosomes in the GnomAD database, including 20,719 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 0.52 (20719 hom., cov: 32)
• Consequence: PROC NM_000312.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.95

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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PROC	NM_000312.4	c.70+386T>C		intron_variant		ENST00000234071.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PROC	ENST00000234071.8	c.70+386T>C		intron_variant		1	NM_000312.4	P1

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78473 AN: 151852 Hom.: 20711 Cov.: 32

Gnomad AFR AF: 0.498

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.653

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.526

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

GnomAD4 genome AF: 0.517 AC: 78525 AN: 151970 Hom.: 20719 Cov.: 32 AF XY: 0.514 AC XY: 38193 AN XY: 74272

Gnomad4 AFR AF: 0.498

Gnomad4 AMR AF: 0.412

Gnomad4 ASJ AF: 0.510

Gnomad4 EAS AF: 0.263

Gnomad4 SAS AF: 0.653

Gnomad4 FIN AF: 0.550

Gnomad4 NFE AF: 0.557

Gnomad4 OTH AF: 0.532

Alfa AF: 0.483 Hom.: 3097

Bravo AF: 0.501

Asia WGS AF: 0.474 AC: 1649 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.12
Dann	Benign	0.14
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs2069910; hg19: chr2-128177974;