Genetic Variant NM_006404.5:c.*16C>A (chr20-35176829-C-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_006404.5(PROCR):c.*16C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000561 in 1,611,156 control chromosomes in the GnomAD database, including 8 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 0.00043 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00057 ( 8 hom. )

Consequence

PROCR
NM_006404.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.369

Publications

45 publications found

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 was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BS2

High Homozygotes in GnomAdExome4 at 8 AR gene

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.*16C>A		3_prime_UTR	Exon 4 of 4	NP_006395.2
	MMP24-AS1-EDEM2	NM_001355008.2		c.-101-10958G>T		intron	N/A	NP_001341937.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PROCR	ENST00000216968.5	TSL:1 MANE Select	c.*16C>A	3_prime_UTR	Exon 4 of 4	ENSP00000216968.3	Q9UNN8
PROCR	ENST00000852804.1		c.*16C>A	3_prime_UTR	Exon 5 of 5	ENSP00000522863.1
PROCR	ENST00000852805.1		c.*16C>A	3_prime_UTR	Exon 5 of 5	ENSP00000522864.1

Frequencies

GnomAD3 genomes

AF:

0.000435

AC:

AN:

151848

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000852

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000412

Gnomad OTH

AF:

0.000960

GnomAD2 exomes

AF:

0.00111

AC:

273

AN:

246476

AF XY:

0.00126

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00151

Gnomad ASJ exome

AF:

0.00311

Gnomad EAS exome

AF:

0.0000554

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000467

Gnomad OTH exome

AF:

0.00199

GnomAD4 exome

AF:

0.000574

AC:

838

AN:

1459188

Hom.:

Cov.:

AF XY:

0.000670

AC XY:

486

AN XY:

725580

show subpopulations

African (AFR)

AF:

0.000478

AC:

AN:

33470

American (AMR)

AF:

0.00138

AC:

AN:

44222

Ashkenazi Jewish (ASJ)

AF:

0.00211

AC:

AN:

26062

East Asian (EAS)

AF:

0.00

AC:

AN:

39662

South Asian (SAS)

AF:

0.00387

AC:

332

AN:

85744

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53236

Middle Eastern (MID)

AF:

0.0118

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.000222

AC:

247

AN:

1110706

Other (OTH)

AF:

0.000978

AC:

AN:

60326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

100

151

201

251

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000434

AC:

AN:

151968

Hom.:

Cov.:

AF XY:

0.000472

AC XY:

AN XY:

74228

show subpopulations

African (AFR)

AF:

0.000121

AC:

AN:

41456

American (AMR)

AF:

0.000851

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5146

South Asian (SAS)

AF:

0.00291

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10530

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000412

AC:

AN:

67964

Other (OTH)

AF:

0.000950

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00122

Hom.:

2631

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

8.6

(source)

DANN

Benign

0.69

PhyloP100

0.37

PromoterAI

-0.0030

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over