rs2069951

Positions:

• chr20-35175961-G-A

Variant summary

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

The NM_006404.5(PROCR):​c.323-207G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0455 in 151,092 control chromosomes in the GnomAD database, including 163 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 0.045 (163 hom., cov: 29)
• Consequence: PROCR NM_006404.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.545

Genes affected

PROCR (HGNC:9452): (protein C receptor) The protein encoded by this gene is a receptor for activated protein C, a serine protease activated by and involved in the blood coagulation pathway. The encoded protein is an N-glycosylated type I membrane protein that enhances the activation of protein C. Mutations in this gene have been associated with venous thromboembolism and myocardial infarction, as well as with late fetal loss during pregnancy. The encoded protein may also play a role in malarial infection and has been associated with cancer. [provided by RefSeq, Jul 2013]

MMP24-AS1-EDEM2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PROCR	NM_006404.5	c.323-207G>A		intron_variant		ENST00000216968.5
MMP24-AS1-EDEM2	NM_001355008.2	c.-101-10090C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PROCR	ENST00000216968.5	c.323-207G>A		intron_variant		1	NM_006404.5	P1
PROCR	ENST00000635377.1	c.223-207G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0455 AC: 6866 AN: 150976 Hom.: 163 Cov.: 29

Gnomad AFR AF: 0.0522

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.0417

Gnomad ASJ AF: 0.0798

Gnomad EAS AF: 0.000777

Gnomad SAS AF: 0.0274

Gnomad FIN AF: 0.0249

Gnomad MID AF: 0.0637

Gnomad NFE AF: 0.0469

Gnomad OTH AF: 0.0544

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

GnomAD4 genome AF: 0.0455 AC: 6870 AN: 151092 Hom.: 163 Cov.: 29 AF XY: 0.0443 AC XY: 3270 AN XY: 73762

Gnomad4 AFR AF: 0.0521

Gnomad4 AMR AF: 0.0417

Gnomad4 ASJ AF: 0.0798

Gnomad4 EAS AF: 0.000779

Gnomad4 SAS AF: 0.0272

Gnomad4 FIN AF: 0.0249

Gnomad4 NFE AF: 0.0469

Gnomad4 OTH AF: 0.0538

Alfa AF: 0.0447 Hom.: 45

Bravo AF: 0.0473

Asia WGS AF: 0.0200 AC: 70 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.42
DANN	Benign	0.56

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: rs2069951; hg19: chr20-33763764;