Genetic Variant NM_002710.4:c.419-1846A>G (chr12-110726610-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_002710.4(PPP1CC):c.419-1846A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,076 control chromosomes in the GnomAD database, including 1,186 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 ( 1186 hom., cov: 32)

Exomes 𝑓: 0.12 ( 0 hom. )

Consequence

PPP1CC
NM_002710.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.444

Publications

1 publications found

Variant links:

Genes affected

PPP1CC (HGNC:9283): (protein phosphatase 1 catalytic subunit gamma) The protein encoded by this gene belongs to the protein phosphatase family, PP1 subfamily. PP1 is an ubiquitous serine/threonine phosphatase that regulates many cellular processes, including cell division. It is expressed in mammalian cells as three closely related isoforms, alpha, beta/delta and gamma, which have distinct localization patterns. This gene encodes the gamma isozyme. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

PPP1CC links:

Genome browser will be placed here

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=-0.85).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1CC	NM_002710.4 link	c.419-1846A>G		intron_variant	Intron 3 of 6	ENST00000335007.10	NP_002701.1	P36873-1A0A024RBP2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1CC	ENST00000335007.10 link	c.419-1846A>G		intron_variant	Intron 3 of 6	1	NM_002710.4	ENSP00000335084.5		P36873-1
PPP1CC	ENST00000550261.5 link	n.105-3915A>G		intron_variant	Intron 1 of 4	5		ENSP00000447528.2		F8W0V8

Frequencies

GnomAD3 genomes

AF:

0.116

AC:

17583

AN:

151924

Hom.:

1185

Cov.:

show subpopulations

Gnomad AFR

AF:

0.184

Gnomad AMI

AF:

0.112

Gnomad AMR

AF:

0.0734

Gnomad ASJ

AF:

0.139

Gnomad EAS

AF:

0.00520

Gnomad SAS

AF:

0.103

Gnomad FIN

AF:

0.0737

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.0985

Gnomad OTH

AF:

0.112

GnomAD4 exome

AF:

0.118

AC:

AN:

Hom.:

Cov.:

AF XY:

0.167

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.115

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.650

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.116

AC:

17601

AN:

152042

Hom.:

1186

Cov.:

AF XY:

0.113

AC XY:

8378

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.184

AC:

7635

AN:

41432

American (AMR)

AF:

0.0732

AC:

1118

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.139

AC:

483

AN:

3468

East Asian (EAS)

AF:

0.00521

AC:

AN:

5180

South Asian (SAS)

AF:

0.102

AC:

493

AN:

4814

European-Finnish (FIN)

AF:

0.0737

AC:

781

AN:

10592

Middle Eastern (MID)

AF:

0.113

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0985

AC:

6695

AN:

67964

Other (OTH)

AF:

0.111

AC:

234

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

783

1565

2348

3130

3913

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

194

388

582

776

970

<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:

0.108

Hom.:

187

Bravo

AF:

0.118

Asia WGS

AF:

0.0620

AC:

218

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

2.8

(source)

DANN

Benign

0.61

PhyloP100

0.44

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