12-10847181-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_007244.3(PRR4):c.287G>A(p.Arg96Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 1,612,768 control chromosomes in the GnomAD database, including 268,556 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.49 ( 20668 hom., cov: 29)

Exomes 𝑓: 0.58 ( 247888 hom. )

Consequence

PRR4
NM_007244.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -3.34

Publications

35 publications found

Variant links:

Genes affected

PRR4 (HGNC:18020): (proline rich 4) This gene encodes a member of the proline-rich protein family that lacks a conserved repetitive domain. This protein may play a role in protective functions in the eye. Alternative splicing result in multiple transcript variants. Read-through transcription also exists between this gene and the upstream PRH1 (proline-rich protein HaeIII subfamily 1) gene. [provided by RefSeq, Feb 2011]

PRR4 links:

ENSG00000275778 (HGNC:):

ENSG00000275778 links:

PRH1 (HGNC:9366): (proline rich protein HaeIII subfamily 1) This gene encodes a member of the heterogeneous family of proline-rich salivary glycoproteins. The encoded preproprotein undergoes proteolytic processing to generate one or more mature isoforms before secretion from the parotid and submandibular/sublingual glands. Multiple distinct alleles of this locus including the parotid isoelectric-focusing variant slow (PIF-s), the parotid acidic protein (Pa), and the double band slow (Db-s) isoforms have been characterized. The reference genome encodes the Db-s allele. Certain alleles of this gene are associated with susceptibility to dental caries. This gene is located in a cluster of closely related salivary proline-rich proteins on chromosome 12. Co-transcription of this gene with adjacent genes has been observed. Alternate splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2015]

PRH1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.3043367E-6).

BP6

Variant 12-10847181-C-T is Benign according to our data. Variant chr12-10847181-C-T is described in ClinVar as Benign. ClinVar VariationId is 3060846.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRR4	NM_007244.3 link	c.287G>A	p.Arg96Gln	missense_variant	Exon 3 of 4	ENST00000228811.8	NP_009175.2	Q16378-1
PRH1-PRR4	NR_037918.2 link	n.1407G>A		non_coding_transcript_exon_variant	Exon 9 of 10
PRR4	NM_001098538.3 link	c.101-46G>A		intron_variant	Intron 2 of 3		NP_001092008.2	Q16378-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PRR4	ENST00000228811.8 link	c.287G>A	p.Arg96Gln	missense_variant	Exon 3 of 4	1	NM_007244.3	ENSP00000228811.4	Q16378-1
ENSG00000275778	ENST00000536668.2 link	n.*241G>A		non_coding_transcript_exon_variant	Exon 9 of 10	5		ENSP00000482961.1	A0A087WZY1
ENSG00000275778	ENST00000536668.2 link	n.*241G>A		3_prime_UTR_variant	Exon 9 of 10	5		ENSP00000482961.1	A0A087WZY1

Frequencies

GnomAD3 genomes

AF:

0.490

AC:

74200

AN:

151578

Hom.:

20673

Cov.:

show subpopulations

Gnomad AFR

AF:

0.209

Gnomad AMI

AF:

0.539

Gnomad AMR

AF:

0.608

Gnomad ASJ

AF:

0.672

Gnomad EAS

AF:

0.708

Gnomad SAS

AF:

0.660

Gnomad FIN

AF:

0.627

Gnomad MID

AF:

0.652

Gnomad NFE

AF:

0.571

Gnomad OTH

AF:

0.533

GnomAD2 exomes

AF:

0.597

AC:

148759

AN:

249200

AF XY:

0.605

show subpopulations

Gnomad AFR exome

AF:

0.200

Gnomad AMR exome

AF:

0.647

Gnomad ASJ exome

AF:

0.669

Gnomad EAS exome

AF:

0.716

Gnomad FIN exome

AF:

0.623

Gnomad NFE exome

AF:

0.583

Gnomad OTH exome

AF:

0.610

GnomAD4 exome

AF:

0.578

AC:

844212

AN:

1461072

Hom.:

247888

Cov.:

AF XY:

0.582

AC XY:

422903

AN XY:

726814

show subpopulations

African (AFR)

AF:

0.200

AC:

6688

AN:

33476

American (AMR)

AF:

0.646

AC:

28872

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.670

AC:

17513

AN:

26120

East Asian (EAS)

AF:

0.729

AC:

28948

AN:

39686

South Asian (SAS)

AF:

0.670

AC:

57661

AN:

86092

European-Finnish (FIN)

AF:

0.618

AC:

33008

AN:

53392

Middle Eastern (MID)

AF:

0.650

AC:

3750

AN:

5766

European-Non Finnish (NFE)

AF:

0.569

AC:

632938

AN:

1111500

Other (OTH)

AF:

0.577

AC:

34834

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

21388

42776

64164

85552

106940

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17598

35196

52794

70392

87990

<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:

0.489

AC:

74201

AN:

151696

Hom.:

20668

Cov.:

AF XY:

0.498

AC XY:

36861

AN XY:

74092

show subpopulations

African (AFR)

AF:

0.209

AC:

8626

AN:

41358

American (AMR)

AF:

0.608

AC:

9267

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.672

AC:

2333

AN:

3470

East Asian (EAS)

AF:

0.708

AC:

3628

AN:

5126

South Asian (SAS)

AF:

0.660

AC:

3157

AN:

4784

European-Finnish (FIN)

AF:

0.627

AC:

6595

AN:

10510

Middle Eastern (MID)

AF:

0.643

AC:

189

AN:

294

European-Non Finnish (NFE)

AF:

0.571

AC:

38787

AN:

67896

Other (OTH)

AF:

0.535

AC:

1127

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1657

3315

4972

6630

8287

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

652

1304

1956

2608

3260

<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:

0.553

Hom.:

66020

Bravo

AF:

0.475

TwinsUK

AF:

0.565

AC:

2095

ALSPAC

AF:

0.567

AC:

2184

ESP6500AA

AF:

0.210

AC:

850

ESP6500EA

AF:

0.579

AC:

4834

ExAC

AF:

0.589

AC:

71210

Asia WGS

AF:

0.642

AC:

2232

AN:

3478

EpiCase

AF:

0.589

EpiControl

AF:

0.589

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PRR4-related disorder

Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.90

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.050

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.0023

T;T

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.00069

LIST_S2

Benign

0.42

.;T

MetaRNN

Benign

0.0000023

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.75

N;.

PhyloP100

-3.3

PrimateAI

Benign

0.25

PROVEAN

Benign

1.4

N;.

REVEL

Benign

0.013

Sift

Benign

0.83

T;.

Sift4G

Benign

0.89

T;T

Polyphen

0.0060

B;.

Vest4

0.045

MPC

0.090

ClinPred

0.0076

GERP RS

-3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.020

gMVP

0.015

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over