rs2069920

Positions:

• chr2-127422070-T-C

Variant summary

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

The NM_000312.4(PROC):​c.237+621T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 152,008 control chromosomes in the GnomAD database, including 11,366 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 0.37 (11366 hom., cov: 33)
• Consequence: PROC NM_000312.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.277

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PROC	NM_000312.4	c.237+621T>C		intron_variant		ENST00000234071.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PROC	ENST00000234071.8	c.237+621T>C		intron_variant		1	NM_000312.4	P1

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56304 AN: 151890 Hom.: 11358 Cov.: 33

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.461

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.371 AC: 56323 AN: 152008 Hom.: 11366 Cov.: 33 AF XY: 0.374 AC XY: 27767 AN XY: 74282

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.533

Gnomad4 ASJ AF: 0.461

Gnomad4 EAS AF: 0.569

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.424

Gnomad4 NFE AF: 0.405

Gnomad4 OTH AF: 0.373

Alfa AF: 0.391 Hom.: 1815

Bravo AF: 0.378

Asia WGS AF: 0.406 AC: 1411 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.1
DANN	Benign	0.55

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: rs2069920; hg19: chr2-128179646;