Genetic Variant PPP1R12B:c.-696A>G (chr1-202462874-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 ENST00000290419.9(PPP1R12B):c.-696A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 984,704 control chromosomes in the GnomAD database, including 113,716 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 0.43 ( 15677 hom., cov: 31)

Exomes 𝑓: 0.48 ( 98039 hom. )

Consequence

PPP1R12B
ENST00000290419.9 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.58

Publications

7 publications found

Variant links:

Genes affected

PPP1R12B (HGNC:7619): (protein phosphatase 1 regulatory subunit 12B) Myosin phosphatase is a protein complex comprised of three subunits: a catalytic subunit (PP1c-delta, protein phosphatase 1, catalytic subunit delta), a large regulatory subunit (MYPT, myosin phosphatase target) and small regulatory subunit (sm-M20). Two isoforms of MYPT have been isolated--MYPT1 and MYPT2, the first of which is widely expressed, and the second of which may be specific to heart, skeletal muscle, and brain. Each of the MYPT isoforms functions to bind PP1c-delta and increase phosphatase activity. This locus encodes both MYTP2 and M20. Alternatively spliced transcript variants encoding different isoforms have been identified. Related pseudogenes have been defined on the Y chromosome. [provided by RefSeq, Oct 2011]

PPP1R12B 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=-0.79).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R12B	NM_002481.4 link	c.1850+13703A>G		intron_variant	Intron 13 of 23	ENST00000608999.6	NP_002472.2	O60237-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1R12B	ENST00000608999.6 link	c.1850+13703A>G		intron_variant	Intron 13 of 23	1	NM_002481.4	ENSP00000476755.1		O60237-1

Frequencies

GnomAD3 genomes

AF:

0.434

AC:

65928

AN:

151846

Hom.:

15668

Cov.:

show subpopulations

Gnomad AFR

AF:

0.253

Gnomad AMI

AF:

0.402

Gnomad AMR

AF:

0.577

Gnomad ASJ

AF:

0.367

Gnomad EAS

AF:

0.707

Gnomad SAS

AF:

0.629

Gnomad FIN

AF:

0.463

Gnomad MID

AF:

0.332

Gnomad NFE

AF:

0.478

Gnomad OTH

AF:

0.424

GnomAD4 exome

AF:

0.483

AC:

402115

AN:

832740

Hom.:

98039

Cov.:

AF XY:

0.484

AC XY:

185948

AN XY:

384578

show subpopulations

African (AFR)

AF:

0.219

AC:

3460

AN:

15778

American (AMR)

AF:

0.631

AC:

621

AN:

984

Ashkenazi Jewish (ASJ)

AF:

0.378

AC:

1945

AN:

5152

East Asian (EAS)

AF:

0.693

AC:

2517

AN:

3630

South Asian (SAS)

AF:

0.602

AC:

9913

AN:

16454

European-Finnish (FIN)

AF:

0.454

AC:

128

AN:

282

Middle Eastern (MID)

AF:

0.398

AC:

645

AN:

1620

European-Non Finnish (NFE)

AF:

0.485

AC:

369433

AN:

761552

Other (OTH)

AF:

0.493

AC:

13453

AN:

27288

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

11067

22134

33201

44268

55335

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14840

29680

44520

59360

74200

<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:

0.434

AC:

65951

AN:

151964

Hom.:

15677

Cov.:

AF XY:

0.439

AC XY:

32583

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.253

AC:

10475

AN:

41464

American (AMR)

AF:

0.578

AC:

8814

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.367

AC:

1272

AN:

3466

East Asian (EAS)

AF:

0.707

AC:

3648

AN:

5162

South Asian (SAS)

AF:

0.628

AC:

3025

AN:

4816

European-Finnish (FIN)

AF:

0.463

AC:

4890

AN:

10552

Middle Eastern (MID)

AF:

0.316

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.478

AC:

32467

AN:

67938

Other (OTH)

AF:

0.427

AC:

900

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1786

3572

5359

7145

8931

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

624

1248

1872

2496

3120

<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:

0.481

Hom.:

5294

Bravo

AF:

0.433

Asia WGS

AF:

0.630

AC:

2189

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

(source)

DANN

Benign

0.84

PhyloP100

1.6

PromoterAI

0.032

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Computational scores

Splicing

Publications

Other links and lift over