chr5-134225648-A-G

Variant names:

• chr5-134225648-A-G
• rs3895755
• NM_002715.4:c.102+112T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002715.4(PPP2CA):​c.102+112T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0751 in 886,418 control chromosomes in the GnomAD database, including 3,189 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 0.099 (880 hom., cov: 32)
  • Exomes 𝑓: 0.070 (2309 hom.)
• Consequence: PPP2CA NM_002715.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.273
• Publications: 5 publications found

Genes affected

PPP2CA (HGNC:9299): (protein phosphatase 2 catalytic subunit alpha) This gene encodes the phosphatase 2A catalytic subunit. Protein phosphatase 2A is one of the four major Ser/Thr phosphatases, and it is implicated in the negative control of cell growth and division. It consists of a common heteromeric core enzyme, which is composed of a catalytic subunit and a constant regulatory subunit, that associates with a variety of regulatory subunits. This gene encodes an alpha isoform of the catalytic subunit. [provided by RefSeq, Jul 2008]

ENSG00000272772 (HGNC:):

MIR3661 (HGNC:38892): (microRNA 3661) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002715.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2CA	NM_002715.4	MANE Select	c.102+112T>C		intron	N/A	NP_002706.1
	PPP2CA	NM_001355019.2		c.-533T>C		upstream_gene	N/A	NP_001341948.1
	MIR3661	NR_037434.1		n.-109A>G		upstream_gene	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2CA	ENST00000481195.6	TSL:1 MANE Select	c.102+112T>C		intron	N/A	ENSP00000418447.1
	ENSG00000272772	ENST00000519718.2	TSL:5	c.102+112T>C		intron	N/A	ENSP00000430774.2
	ENSG00000273345	ENST00000703317.1		n.*73+17244T>C		intron	N/A	ENSP00000515260.1

Frequencies

GnomAD3 genomes AF: 0.0991 AC: 14989 AN: 151244 Hom.: 873 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.0319

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.0836

Gnomad EAS AF: 0.0552

Gnomad SAS AF: 0.0988

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.132

Gnomad NFE AF: 0.0655

Gnomad OTH AF: 0.120

GnomAD4 exome AF: 0.0701 AC: 51522 AN: 735054 Hom.: 2309 Cov.: 10 AF XY: 0.0712 AC XY: 26512 AN XY: 372502

African (AFR) AF: 0.140 AC: 2162 AN: 15434

American (AMR) AF: 0.175 AC: 2630 AN: 15038

Ashkenazi Jewish (ASJ) AF: 0.0721 AC: 1017 AN: 14100

East Asian (EAS) AF: 0.0498 AC: 1340 AN: 26926

South Asian (SAS) AF: 0.109 AC: 5364 AN: 49266

European-Finnish (FIN) AF: 0.129 AC: 3683 AN: 28604

Middle Eastern (MID) AF: 0.0948 AC: 301 AN: 3176

European-Non Finnish (NFE) AF: 0.0588 AC: 32302 AN: 548928

Other (OTH) AF: 0.0811 AC: 2723 AN: 33582

GnomAD4 genome AF: 0.0992 AC: 15012 AN: 151364 Hom.: 880 Cov.: 32 AF XY: 0.105 AC XY: 7760 AN XY: 73994

African (AFR) AF: 0.130 AC: 5342 AN: 41180

American (AMR) AF: 0.156 AC: 2379 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0836 AC: 290 AN: 3468

East Asian (EAS) AF: 0.0547 AC: 279 AN: 5096

South Asian (SAS) AF: 0.0990 AC: 475 AN: 4796

European-Finnish (FIN) AF: 0.142 AC: 1486 AN: 10490

Middle Eastern (MID) AF: 0.131 AC: 37 AN: 282

European-Non Finnish (NFE) AF: 0.0655 AC: 4440 AN: 67784

Other (OTH) AF: 0.121 AC: 255 AN: 2100

Alfa AF: 0.0414 Hom.: 38

Bravo AF: 0.102

Asia WGS AF: 0.0980 AC: 341 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.47
PhyloP100		-0.27
PromoterAI		0.011	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3895755; hg19: chr5-133561339;