chr1-202436543-A-G

Variant names:

• chr1-202436543-A-G
• rs2741853
• NM_002481.4:c.1255-1278A>G

Variant summary

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

The NM_002481.4(PPP1R12B):​c.1255-1278A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 152,010 control chromosomes in the GnomAD database, including 33,405 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 0.66 (33405 hom., cov: 31)
• Consequence: PPP1R12B NM_002481.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.871
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002481.4. 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
	PPP1R12B	NM_002481.4	MANE Select	c.1255-1278A>G		intron	N/A	NP_002472.2
	PPP1R12B	NM_001331029.2		c.1255-1278A>G		intron	N/A	NP_001317958.1
	PPP1R12B	NM_001410283.1		c.1255-1278A>G		intron	N/A	NP_001397212.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R12B	ENST00000608999.6	TSL:1 MANE Select	c.1255-1278A>G		intron	N/A	ENSP00000476755.1
	PPP1R12B	ENST00000480184.5	TSL:1	c.1255-1278A>G		intron	N/A	ENSP00000417159.1
	PPP1R12B	ENST00000356764.6	TSL:1	c.1142-1278A>G		intron	N/A	ENSP00000349206.2

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100466 AN: 151892 Hom.: 33370 Cov.: 31

Gnomad AFR AF: 0.644

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.740

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.776

Gnomad SAS AF: 0.732

Gnomad FIN AF: 0.632

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.652

Gnomad OTH AF: 0.658

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

GnomAD4 genome AF: 0.661 AC: 100553 AN: 152010 Hom.: 33405 Cov.: 31 AF XY: 0.660 AC XY: 49027 AN XY: 74292

African (AFR) AF: 0.644 AC: 26674 AN: 41434

American (AMR) AF: 0.741 AC: 11316 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.579 AC: 2009 AN: 3468

East Asian (EAS) AF: 0.775 AC: 4015 AN: 5178

South Asian (SAS) AF: 0.732 AC: 3524 AN: 4816

European-Finnish (FIN) AF: 0.632 AC: 6670 AN: 10546

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.652 AC: 44336 AN: 67976

Other (OTH) AF: 0.658 AC: 1388 AN: 2108

Alfa AF: 0.655 Hom.: 94694

Bravo AF: 0.666

Asia WGS AF: 0.736 AC: 2558 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.18
DANN	Benign	0.37
PhyloP100		-0.87
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: rs2741853; hg19: chr1-202405671; COSMIC: COSV61114821; COSMIC: COSV61114821;