Genetic Variant PPP1R11:c.-99C>A (chr6-30067312-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_021959.3(PPP1R11):c.-99C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0939 in 1,280,210 control chromosomes in the GnomAD database, including 6,447 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 0.086 ( 649 hom., cov: 32)

Exomes 𝑓: 0.095 ( 5798 hom. )

Consequence

PPP1R11
NM_021959.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.176

Publications

8 publications found

Variant links:

Genes affected

PPP1R11 (HGNC:9285): (protein phosphatase 1 regulatory inhibitor subunit 11) This gene encodes a specific inhibitor of protein phosphatase-1 (PP1) with a differential sensitivity toward the metal-independent and metal-dependent forms of PP1. The gene is located within the major histocompatibility complex class I region on chromosome 6. [provided by RefSeq, Jul 2008]

PPP1R11 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=-0.69).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PPP1R11	NM_021959.3 link	c.-99C>A	5_prime_UTR_variant	Exon 1 of 3	ENST00000376772.8	NP_068778.1	O60927A2BEK1
PPP1R11	XM_047419279.1 link	c.-99C>A	5_prime_UTR_variant	Exon 2 of 4		XP_047275235.1
PPP1R11	XM_047419280.1 link	c.-99C>A	5_prime_UTR_variant	Exon 3 of 5		XP_047275236.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PPP1R11	ENST00000376772.8 link	c.-99C>A	5_prime_UTR_variant	Exon 1 of 3	1	NM_021959.3	ENSP00000365963.3	O60927
PPP1R11	ENST00000376769.6 link	c.-330C>A	5_prime_UTR_variant	Exon 1 of 4	2		ENSP00000365960.2	Q5SRK2
PPP1R11	ENST00000376773.5 link	c.-88+303C>A	intron_variant	Intron 1 of 2	3		ENSP00000365964.1	Q5SRK2
PPP1R11	ENST00000376765.6 link	c.-515C>A	upstream_gene_variant		3		ENSP00000365956.2	Q5SRK2

Frequencies

GnomAD3 genomes

AF:

0.0860

AC:

13076

AN:

152110

Hom.:

647

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0638

Gnomad AMI

AF:

0.0439

Gnomad AMR

AF:

0.149

Gnomad ASJ

AF:

0.0668

Gnomad EAS

AF:

0.0387

Gnomad SAS

AF:

0.108

Gnomad FIN

AF:

0.0778

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0901

Gnomad OTH

AF:

0.0915

GnomAD4 exome

AF:

0.0949

AC:

107062

AN:

1127984

Hom.:

5798

Cov.:

AF XY:

0.0960

AC XY:

54365

AN XY:

566390

show subpopulations

African (AFR)

AF:

0.0559

AC:

1486

AN:

26572

American (AMR)

AF:

0.180

AC:

7073

AN:

39344

Ashkenazi Jewish (ASJ)

AF:

0.0616

AC:

1349

AN:

21906

East Asian (EAS)

AF:

0.0626

AC:

2305

AN:

36802

South Asian (SAS)

AF:

0.138

AC:

10147

AN:

73770

European-Finnish (FIN)

AF:

0.0861

AC:

4423

AN:

51364

Middle Eastern (MID)

AF:

0.0597

AC:

298

AN:

4988

European-Non Finnish (NFE)

AF:

0.0921

AC:

75951

AN:

824668

Other (OTH)

AF:

0.0830

AC:

4030

AN:

48570

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

4564

9128

13693

18257

22821

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2668

5336

8004

10672

13340

<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:

0.0861

AC:

13100

AN:

152226

Hom.:

649

Cov.:

AF XY:

0.0864

AC XY:

6429

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.0639

AC:

2652

AN:

41532

American (AMR)

AF:

0.149

AC:

2277

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0668

AC:

232

AN:

3472

East Asian (EAS)

AF:

0.0388

AC:

201

AN:

5178

South Asian (SAS)

AF:

0.111

AC:

533

AN:

4820

European-Finnish (FIN)

AF:

0.0778

AC:

825

AN:

10600

Middle Eastern (MID)

AF:

0.0685

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0901

AC:

6129

AN:

68016

Other (OTH)

AF:

0.0905

AC:

191

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

599

1198

1797

2396

2995

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

154

308

462

616

770

<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:

0.0852

Hom.:

1236

Bravo

AF:

0.0907

Asia WGS

AF:

0.0720

AC:

249

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

6.6

(source)

DANN

Benign

0.84

PhyloP100

-0.18

PromoterAI

-0.11

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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