rs2069951

Variant names:

• chr20-35175961-G-A
• rs2069951
• NM_006404.5:c.323-207G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PROCR	NM_006404.5	c.323-207G>A		intron_variant	Intron 2 of 3	ENST00000216968.5	NP_006395.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PROCR	ENST00000216968.5	c.323-207G>A		intron_variant	Intron 2 of 3	1	NM_006404.5	ENSP00000216968.3
PROCR	ENST00000635377.1	c.221-207G>A		intron_variant	Intron 1 of 3	5		ENSP00000489117.1

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

African (AFR) AF: 0.0521 AC: 2143 AN: 41130

American (AMR) AF: 0.0417 AC: 633 AN: 15188

Ashkenazi Jewish (ASJ) AF: 0.0798 AC: 277 AN: 3470

East Asian (EAS) AF: 0.000779 AC: 4 AN: 5134

South Asian (SAS) AF: 0.0272 AC: 130 AN: 4772

European-Finnish (FIN) AF: 0.0249 AC: 258 AN: 10352

Middle Eastern (MID) AF: 0.0685 AC: 20 AN: 292

European-Non Finnish (NFE) AF: 0.0469 AC: 3180 AN: 67744

Other (OTH) AF: 0.0538 AC: 113 AN: 2100

Alfa AF: 0.0468 Hom.: 87

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
PhyloP100		-0.55
PromoterAI		0.011	Neutral
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs2069951; hg19: chr20-33763764;