dbSNP rs1107110: PPP4R4:c.2284+100A>G (chr14-94265573-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_058237.2(PPP4R4):c.2284+100A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 1,058,674 control chromosomes in the GnomAD database, including 24,170 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 0.20 ( 3696 hom., cov: 32)

Exomes 𝑓: 0.19 ( 20474 hom. )

Consequence

PPP4R4
NM_058237.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.198

Publications

6 publications found

Variant links:

Genes affected

PPP4R4 (HGNC:23788): (protein phosphatase 4 regulatory subunit 4) The protein encoded by this gene is a HEAT-like repeat-containing protein. The HEAT repeat is a tandemly repeated, 37-47 amino acid long module occurring in a number of cytoplasmic proteins. Arrays of HEAT repeats form a rod-like helical structure and appear to function as protein-protein interaction surfaces. The repeat-containing region of this protein has some similarity to the constant regulatory domain of the protein phosphatase 2A PR65/A subunit. The encoded protein binds protein serine/threonine phosphatase 4c in the cytoplasm. [provided by RefSeq, Jan 2017]

PPP4R4 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=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP4R4	NM_058237.2 link	c.2284+100A>G		intron_variant	Intron 21 of 24	ENST00000304338.8	NP_478144.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP4R4	ENST00000304338.8 link	c.2284+100A>G		intron_variant	Intron 21 of 24	1	NM_058237.2	ENSP00000305924.3		Q6NUP7-1

Frequencies

GnomAD3 genomes

AF:

0.204

AC:

31071

AN:

151948

Hom.:

3695

Cov.:

show subpopulations

Gnomad AFR

AF:

0.235

Gnomad AMI

AF:

0.192

Gnomad AMR

AF:

0.153

Gnomad ASJ

AF:

0.178

Gnomad EAS

AF:

0.587

Gnomad SAS

AF:

0.254

Gnomad FIN

AF:

0.209

Gnomad MID

AF:

0.196

Gnomad NFE

AF:

0.166

Gnomad OTH

AF:

0.207

GnomAD4 exome

AF:

0.194

AC:

175649

AN:

906608

Hom.:

20474

AF XY:

0.195

AC XY:

91106

AN XY:

466440

show subpopulations

African (AFR)

AF:

0.237

AC:

4843

AN:

20412

American (AMR)

AF:

0.163

AC:

5480

AN:

33632

Ashkenazi Jewish (ASJ)

AF:

0.171

AC:

3376

AN:

19700

East Asian (EAS)

AF:

0.587

AC:

20278

AN:

34556

South Asian (SAS)

AF:

0.256

AC:

16424

AN:

64064

European-Finnish (FIN)

AF:

0.192

AC:

9570

AN:

49974

Middle Eastern (MID)

AF:

0.236

AC:

1067

AN:

4524

European-Non Finnish (NFE)

AF:

0.166

AC:

106041

AN:

638436

Other (OTH)

AF:

0.207

AC:

8570

AN:

41310

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

6980

13960

20941

27921

34901

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3054

6108

9162

12216

15270

<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:

0.204

AC:

31096

AN:

152066

Hom.:

3696

Cov.:

AF XY:

0.209

AC XY:

15570

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.235

AC:

9747

AN:

41472

American (AMR)

AF:

0.153

AC:

2341

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.178

AC:

616

AN:

3464

East Asian (EAS)

AF:

0.588

AC:

3031

AN:

5156

South Asian (SAS)

AF:

0.253

AC:

1218

AN:

4812

European-Finnish (FIN)

AF:

0.209

AC:

2210

AN:

10582

Middle Eastern (MID)

AF:

0.207

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.166

AC:

11261

AN:

67974

Other (OTH)

AF:

0.206

AC:

436

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1204

2407

3611

4814

6018

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

346

692

1038

1384

1730

<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:

0.119

Hom.:

217

Bravo

AF:

0.204

Asia WGS

AF:

0.367

AC:

1274

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.6

(source)

DANN

Benign

0.68

PhyloP100

-0.20

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