rs867186

Variant names:

• chr20-35176751-A-G
• rs867186
• NM_006404.5:c.655A>G

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 202 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 (MetaRNN=0.0013577342).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006404.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PROCR	NM_006404.5	MANE Select	c.655A>G	p.Ser219Gly	missense	Exon 4 of 4	NP_006395.2
	MMP24-AS1-EDEM2	NM_001355008.2		c.-101-10880T>C		intron	N/A	NP_001341937.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PROCR	ENST00000216968.5	TSL:1 MANE Select	c.655A>G	p.Ser219Gly	missense	Exon 4 of 4	ENSP00000216968.3	Q9UNN8
	PROCR	ENST00000852804.1		c.655A>G	p.Ser219Gly	missense	Exon 5 of 5	ENSP00000522863.1
	PROCR	ENST00000852805.1		c.655A>G	p.Ser219Gly	missense	Exon 5 of 5	ENSP00000522864.1

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

GnomAD2 exomes AF: 0.103 AC: 25922 AN: 250950 AF XY: 0.109

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 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

African (AFR) AF: 0.0889 AC: 2976 AN: 33480

American (AMR) AF: 0.0430 AC: 1920 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 2960 AN: 26124

East Asian (EAS) AF: 0.0610 AC: 2420 AN: 39686

South Asian (SAS) AF: 0.177 AC: 15240 AN: 86180

European-Finnish (FIN) AF: 0.133 AC: 7103 AN: 53400

Middle Eastern (MID) AF: 0.119 AC: 689 AN: 5768

European-Non Finnish (NFE) AF: 0.0919 AC: 102192 AN: 1111890

Other (OTH) AF: 0.0991 AC: 5982 AN: 60390

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

African (AFR) AF: 0.0920 AC: 3821 AN: 41526

American (AMR) AF: 0.0702 AC: 1074 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 426 AN: 3472

East Asian (EAS) AF: 0.0766 AC: 394 AN: 5142

South Asian (SAS) AF: 0.159 AC: 767 AN: 4812

European-Finnish (FIN) AF: 0.134 AC: 1419 AN: 10602

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0964 AC: 6558 AN: 68006

Other (OTH) AF: 0.0980 AC: 207 AN: 2112

Alfa AF: 0.0978 Hom.: 3498

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 v4.9

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
PhyloP100		0.10
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
PromoterAI		-0.022	Neutral
Varity_R		0.043
gMVP		0.33
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs867186; hg19: chr20-33764554; COSMIC: COSV53826500; COSMIC: COSV53826500;