1-202523023-A-G

Variant names:

• chr1-202523023-A-G
• rs7522991
• NM_002481.4:c.2490+26201A>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.2490+26201A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 152,052 control chromosomes in the GnomAD database, including 15,699 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 (15699 hom., cov: 32)
• Consequence: PPP1R12B NM_002481.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0410
• Publications: 2 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.688 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.2490+26201A>G		intron	N/A	NP_002472.2
	PPP1R12B	NM_001331029.2		c.2673+26201A>G		intron	N/A	NP_001317958.1
	PPP1R12B	NM_001410283.1		c.2490+26201A>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.2490+26201A>G		intron	N/A	ENSP00000476755.1
	PPP1R12B	ENST00000290419.9	TSL:1	c.168+26201A>G		intron	N/A	ENSP00000484005.1
	PPP1R12B	ENST00000491336.5	TSL:1	c.168+26201A>G		intron	N/A	ENSP00000480852.1

Frequencies

GnomAD3 genomes AF: 0.435 AC: 66031 AN: 151934 Hom.: 15690 Cov.: 32

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.630

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.327

Gnomad NFE AF: 0.478

Gnomad OTH AF: 0.424

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

GnomAD4 genome AF: 0.434 AC: 66056 AN: 152052 Hom.: 15699 Cov.: 32 AF XY: 0.439 AC XY: 32613 AN XY: 74318

African (AFR) AF: 0.255 AC: 10569 AN: 41470

American (AMR) AF: 0.577 AC: 8820 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 1273 AN: 3472

East Asian (EAS) AF: 0.707 AC: 3659 AN: 5172

South Asian (SAS) AF: 0.629 AC: 3025 AN: 4812

European-Finnish (FIN) AF: 0.463 AC: 4887 AN: 10562

Middle Eastern (MID) AF: 0.310 AC: 90 AN: 290

European-Non Finnish (NFE) AF: 0.478 AC: 32464 AN: 67960

Other (OTH) AF: 0.427 AC: 902 AN: 2114

Alfa AF: 0.469 Hom.: 2992

Bravo AF: 0.433

Asia WGS AF: 0.627 AC: 2175 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.7
DANN	Benign	0.65
PhyloP100		0.041
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: rs7522991; hg19: chr1-202492151;