Variant rs867186 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.105

Variant links:

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]

PROCR links:

MMP24-AS1-EDEM2 (HGNC:):

MMP24-AS1-EDEM2 links:

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ACMG classification

Classification made for transcript

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	Protein	UniProt
PROCR	NM_006404.5 linkuse as main transcript	c.655A>G	p.Ser219Gly	missense_variant	4/4	ENST00000216968.5	NP_006395.2	Q9UNN8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PROCR	ENST00000216968.5 linkuse as main transcript	c.655A>G	p.Ser219Gly	missense_variant	4/4	1	NM_006404.5	ENSP00000216968.3	Q9UNN8
PROCR	ENST00000635377.1 linkuse as main transcript	c.499+305A>G		intron_variant		5		ENSP00000489117.1	A0A0U1RQQ4
PROCR	ENST00000634509.1 linkuse as main transcript	c.94+305A>G		intron_variant		3		ENSP00000489456.1	A0A0U1RRC4

Frequencies

GnomAD3 genomes

AF:

0.0968

AC:

14725

AN:

152054

Hom.:

788

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0994

AC XY:

72304

AN XY:

727064

show subpopulations

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.:

AF XY:

0.100

AC XY:

7457

AN XY:

74396

show subpopulations

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

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.29

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.64

MetaRNN

Benign

0.0014

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.6

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.66

REVEL

Benign

0.057

Sift

Benign

0.031

Sift4G

Uncertain

0.050

Polyphen

0.20

Vest4

0.040

MPC

0.49

ClinPred

0.0049

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over