chr1-202401869-C-T

Variant names:

• chr1-202401869-C-T
• rs11583656
• NM_002481.4:c.292-14918C>T

Variant summary

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

The NM_002481.4(PPP1R12B):​c.292-14918C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,130 control chromosomes in the GnomAD database, including 1,342 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 0.13 (1342 hom., cov: 31)
• Consequence: PPP1R12B NM_002481.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0450
• Publications: 4 publications found

Genes affected

PPP1R12B (HGNC:7619): (protein phosphatase 1 regulatory subunit 12B) Myosin phosphatase is a protein complex comprised of three subunits: a catalytic subunit (PP1c-delta, protein phosphatase 1, catalytic subunit delta), a large regulatory subunit (MYPT, myosin phosphatase target) and small regulatory subunit (sm-M20). Two isoforms of MYPT have been isolated--MYPT1 and MYPT2, the first of which is widely expressed, and the second of which may be specific to heart, skeletal muscle, and brain. Each of the MYPT isoforms functions to bind PP1c-delta and increase phosphatase activity. This locus encodes both MYTP2 and M20. Alternatively spliced transcript variants encoding different isoforms have been identified. Related pseudogenes have been defined on the Y chromosome. [provided by RefSeq, Oct 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R12B	NM_002481.4	c.292-14918C>T		intron_variant	Intron 1 of 23	ENST00000608999.6	NP_002472.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1R12B	ENST00000608999.6	c.292-14918C>T		intron_variant	Intron 1 of 23	1	NM_002481.4	ENSP00000476755.1

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19181 AN: 152012 Hom.: 1341 Cov.: 31

Gnomad AFR AF: 0.0679

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.0693

Gnomad SAS AF: 0.0947

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.126 AC: 19191 AN: 152130 Hom.: 1342 Cov.: 31 AF XY: 0.124 AC XY: 9220 AN XY: 74344

African (AFR) AF: 0.0679 AC: 2821 AN: 41522

American (AMR) AF: 0.114 AC: 1746 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 675 AN: 3468

East Asian (EAS) AF: 0.0692 AC: 358 AN: 5170

South Asian (SAS) AF: 0.0952 AC: 459 AN: 4822

European-Finnish (FIN) AF: 0.166 AC: 1753 AN: 10564

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10919 AN: 67984

Other (OTH) AF: 0.149 AC: 315 AN: 2114

Alfa AF: 0.152 Hom.: 2394

Bravo AF: 0.120

Asia WGS AF: 0.0780 AC: 271 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	8.5
DANN	Benign	0.69
PhyloP100		-0.045
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: rs11583656; hg19: chr1-202370997;