chr1-202463032-T-G

Position:

• chr1-202463032-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000290419.9(PPP1R12B):​c.-538T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 984,590 control chromosomes in the GnomAD database, including 113,748 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 0.43 (15686 hom., cov: 32)
  • Exomes 𝑓: 0.48 (98062 hom.)
• Consequence: PPP1R12B ENST00000290419.9 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.716

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP1R12B	NM_002481.4	c.1850+13861T>G		intron_variant		ENST00000608999.6	NP_002472.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP1R12B	ENST00000608999.6	c.1850+13861T>G		intron_variant		1	NM_002481.4	ENSP00000476755	A2

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65967 AN: 151980 Hom.: 15677 Cov.: 32

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.707

Gnomad SAS AF: 0.630

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.478

Gnomad OTH AF: 0.423

GnomAD4 exome AF: 0.483 AC: 402016 AN: 832492 Hom.: 98062 Cov.: 31 AF XY: 0.484 AC XY: 185908 AN XY: 384464

Gnomad4 AFR exome AF: 0.219

Gnomad4 AMR exome AF: 0.632

Gnomad4 ASJ exome AF: 0.377

Gnomad4 EAS exome AF: 0.693

Gnomad4 SAS exome AF: 0.603

Gnomad4 FIN exome AF: 0.449

Gnomad4 NFE exome AF: 0.485

Gnomad4 OTH exome AF: 0.493

GnomAD4 genome AF: 0.434 AC: 65990 AN: 152098 Hom.: 15686 Cov.: 32 AF XY: 0.438 AC XY: 32584 AN XY: 74342

Gnomad4 AFR AF: 0.253

Gnomad4 AMR AF: 0.578

Gnomad4 ASJ AF: 0.366

Gnomad4 EAS AF: 0.706

Gnomad4 SAS AF: 0.629

Gnomad4 FIN AF: 0.462

Gnomad4 NFE AF: 0.478

Gnomad4 OTH AF: 0.426

Alfa AF: 0.394 Hom.: 2841

Bravo AF: 0.433

Asia WGS AF: 0.630 AC: 2189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.67

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

LitVar

Other links and lift over

dbSNP: rs3767421; hg19: chr1-202432160; COSMIC: COSV51782977;