rs11000671

Variant names:

• chr10-73480219-C-A
• rs11000671
• NM_021132.4:c.86-702G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-73480219-C-A
• chr10-73480219-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021132.4(PPP3CB):​c.86-702G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000661 in 151,330 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 (0 hom., cov: 32)
• Consequence: PPP3CB NM_021132.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.99
• Publications: 0 publications found

Genes affected

PPP3CB (HGNC:9315): (protein phosphatase 3 catalytic subunit beta) Enables several functions, including calmodulin binding activity; calmodulin-dependent protein phosphatase activity; and protein phosphatase 2B binding activity. Involved in calcineurin-NFAT signaling cascade; positive regulation of transcription by RNA polymerase II; and protein dephosphorylation. Located in cytoplasm. Part of calcineurin complex. Implicated in aortic valve stenosis. Biomarker of focal segmental glomerulosclerosis and schizophrenia. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021132.4. 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
	PPP3CB	NM_021132.4	MANE Select	c.86-702G>T		intron	N/A	NP_066955.1
	PPP3CB	NM_001142353.3		c.86-702G>T		intron	N/A	NP_001135825.1
	PPP3CB	NM_001142354.3		c.86-702G>T		intron	N/A	NP_001135826.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP3CB	ENST00000360663.10	TSL:1 MANE Select	c.86-702G>T		intron	N/A	ENSP00000353881.5
	PPP3CB	ENST00000394829.6	TSL:1	c.86-702G>T		intron	N/A	ENSP00000378306.2
	PPP3CB	ENST00000394828.6	TSL:1	c.86-702G>T		intron	N/A	ENSP00000378305.2

Frequencies

GnomAD3 genomes AF: 0.00000661 AC: 1 AN: 151216 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00000661 AC: 1 AN: 151330 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 73994

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 40926

American (AMR) AF: 0.00 AC: 0 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10536

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67858

Other (OTH) AF: 0.00 AC: 0 AN: 2106

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.085
DANN	Benign	0.64
PhyloP100		-3.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs11000671; hg19: chr10-75239977;