Genetic Variant PRB2:c.65-68T>C (chr12-11394598-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006248.4(PRB2):c.65-68T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.052 in 1,569,676 control chromosomes in the GnomAD database, including 6,127 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 0.12 ( 2449 hom., cov: 31)

Exomes 𝑓: 0.045 ( 3678 hom. )

Consequence

PRB2
NM_006248.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0750

Publications

8 publications found

Variant links:

Genes affected

PRB2 (HGNC:9338): (proline rich protein BstNI subfamily 2) This gene encodes a member of the heterogeneous family of basic, proline-rich, human salivary glycoproteins. The encoded preproprotein undergoes proteolytic processing to generate one or more mature isoforms before secretion from the parotid glands. Multiple alleles of this gene exhibiting variations in the length of the tandem repeats, polymorphic cleavage sites and polymorphic stop codons have been identified. This gene is located in a cluster of closely related salivary proline-rich proteins on chromosome 12. [provided by RefSeq, May 2023]

PRB2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006248.4. 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
	PRB2	NM_006248.4	MANE Select	c.65-68T>C		intron	N/A	NP_006239.3	P02812

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRB2	ENST00000389362.6	TSL:5 MANE Select	c.65-68T>C		intron	N/A	ENSP00000374013.4	P02812
	PRB2	ENST00000545829.1	TSL:4	n.365-68T>C		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.121

AC:

18348

AN:

152058

Hom.:

2444

Cov.:

show subpopulations

Gnomad AFR

AF:

0.322

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.113

Gnomad ASJ

AF:

0.0265

Gnomad EAS

AF:

0.0946

Gnomad SAS

AF:

0.124

Gnomad FIN

AF:

0.00753

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0266

Gnomad OTH

AF:

0.0995

GnomAD4 exome

AF:

0.0446

AC:

63265

AN:

1417500

Hom.:

3678

AF XY:

0.0453

AC XY:

32079

AN XY:

707676

show subpopulations

African (AFR)

AF:

0.336

AC:

11023

AN:

32764

American (AMR)

AF:

0.123

AC:

5509

AN:

44620

Ashkenazi Jewish (ASJ)

AF:

0.0224

AC:

578

AN:

25830

East Asian (EAS)

AF:

0.0801

AC:

3158

AN:

39422

South Asian (SAS)

AF:

0.116

AC:

9903

AN:

85414

European-Finnish (FIN)

AF:

0.00918

AC:

488

AN:

53148

Middle Eastern (MID)

AF:

0.0448

AC:

255

AN:

5686

European-Non Finnish (NFE)

AF:

0.0271

AC:

29088

AN:

1071778

Other (OTH)

AF:

0.0555

AC:

3263

AN:

58838

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

2994

5989

8983

11978

14972

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1414

2828

4242

5656

7070

<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:

0.121

AC:

18381

AN:

152176

Hom.:

2449

Cov.:

AF XY:

0.119

AC XY:

8884

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.322

AC:

13354

AN:

41478

American (AMR)

AF:

0.113

AC:

1729

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0265

AC:

AN:

3468

East Asian (EAS)

AF:

0.0944

AC:

489

AN:

5180

South Asian (SAS)

AF:

0.125

AC:

600

AN:

4818

European-Finnish (FIN)

AF:

0.00753

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0266

AC:

1807

AN:

67992

Other (OTH)

AF:

0.0980

AC:

207

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

663

1326

1989

2652

3315

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

178

356

534

712

890

<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:

0.0532

Hom.:

2344

Bravo

AF:

0.137

Asia WGS

AF:

0.0860

AC:

299

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

8.6

(source)

DANN

Benign

0.81

PhyloP100

0.075

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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