rs867186

chr20-35176751-A-G

Variant summary

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

The NM_006404.5(PROCR):c.655A>G(p.Ser219Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0968 in 1,613,772 control chromosomes in the GnomAD database, including 8,351 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.097 (803 hom., cov: 32)
  • Exomes 𝑓: 0.097 (7548 hom.)
• Consequence: PROCR NM_006404.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.105

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 (MetaRNN=0.0013577342).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PROCR	NM_006404.5	c.655A>G	p.Ser219Gly	missense_variant	4/4	ENST00000216968.5
MMP24-AS1-EDEM2	NM_001355008.2	c.-101-10880T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PROCR	ENST00000216968.5	c.655A>G	p.Ser219Gly	missense_variant	4/4	1	NM_006404.5	P1
PROCR	ENST00000634509.1	c.94+305A>G		intron_variant		3
PROCR	ENST00000635377.1	c.501+305A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0968 AC: 14725 AN: 152054 Hom.: 788 Cov.: 32

Gnomad AFR AF: 0.0912

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.0705

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.0770

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0965

Gnomad OTH AF: 0.0943

GnomAD3 exomes AF: 0.103 AC: 25922 AN: 250950 Hom.: 1619 AF XY: 0.109 AC XY: 14826 AN XY: 135656

Gnomad AFR exome AF: 0.0927

Gnomad AMR exome AF: 0.0403

Gnomad ASJ exome AF: 0.112

Gnomad EAS exome AF: 0.0845

Gnomad SAS exome AF: 0.172

Gnomad FIN exome AF: 0.133

Gnomad NFE exome AF: 0.102

Gnomad OTH exome AF: 0.102

GnomAD4 exome AF: 0.0968 AC: 141482 AN: 1461600 Hom.: 7548 Cov.: 36 AF XY: 0.0994 AC XY: 72304 AN XY: 727064

Gnomad4 AFR exome AF: 0.0889

Gnomad4 AMR exome AF: 0.0430

Gnomad4 ASJ exome AF: 0.113

Gnomad4 EAS exome AF: 0.0610

Gnomad4 SAS exome AF: 0.177

Gnomad4 FIN exome AF: 0.133

Gnomad4 NFE exome AF: 0.0919

Gnomad4 OTH exome AF: 0.0991

GnomAD4 genome AF: 0.0970 AC: 14768 AN: 152172 Hom.: 803 Cov.: 32 AF XY: 0.100 AC XY: 7457 AN XY: 74396

Gnomad4 AFR AF: 0.0920

Gnomad4 AMR AF: 0.0702

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.0766

Gnomad4 SAS AF: 0.159

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.0964

Gnomad4 OTH AF: 0.0980

Alfa AF: 0.0979 Hom.: 1947

Bravo AF: 0.0892

TwinsUK AF: 0.0882 AC: 327

ALSPAC AF: 0.0908 AC: 350

ESP6500AA AF: 0.0965 AC: 425

ESP6500EA AF: 0.101 AC: 865

ExAC AF: 0.108 AC: 13092

Asia WGS AF: 0.137 AC: 475 AN: 3478

EpiCase AF: 0.0985

EpiControl AF: 0.101

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.70
Cadd	Benign	17
Dann	Uncertain	0.99
DEOGEN2	Benign	0.29	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.64	T
MetaRNN	Benign	0.0014	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.6	L
MutationTaster	Benign	4.3e-8	P;P;P
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.66	N
REVEL	Benign	0.057
Sift	Benign	0.031	D
Sift4G	Uncertain	0.050	T
Polyphen		0.20	B
Vest4		0.040
MPC		0.49
ClinPred		0.0049	T
GERP RS		-2.6
Varity_R		0.043
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs867186; hg19: chr20-33764554; COSMIC: COSV53826500; COSMIC: COSV53826500;