rs2069912

Variant names:

• chr2-127420615-T-C
• rs2069912
• NM_000312.4:c.70+603T>C

Your query was ambiguous. Multiple possible variants found:

• chr2-127420615-T-C
• chr2-127420615-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+603T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 151,782 control chromosomes in the GnomAD database, including 6,174 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 0.28 (6174 hom., cov: 31)
• Consequence: PROC NM_000312.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PROC	NM_000312.4	c.70+603T>C		intron_variant	Intron 2 of 8	ENST00000234071.8	NP_000303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PROC	ENST00000234071.8	c.70+603T>C		intron_variant	Intron 2 of 8	1	NM_000312.4	ENSP00000234071.4

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42556 AN: 151664 Hom.: 6153 Cov.: 31

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.281 AC: 42624 AN: 151782 Hom.: 6174 Cov.: 31 AF XY: 0.285 AC XY: 21148 AN XY: 74146

Gnomad4 AFR AF: 0.297

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.429

Gnomad4 SAS AF: 0.467

Gnomad4 FIN AF: 0.289

Gnomad4 NFE AF: 0.267

Gnomad4 OTH AF: 0.284

Alfa AF: 0.248 Hom.: 4932

Bravo AF: 0.271

Asia WGS AF: 0.445 AC: 1547 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.6
DANN	Benign	0.77

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: rs2069912; hg19: chr2-128178191;