rs697455

Variant names:

• chr1-202542948-A-G
• rs697455
• NM_002481.4:c.2491-15929A>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.2491-15929A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0306 in 152,228 control chromosomes in the GnomAD database, including 189 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 0.031 (189 hom., cov: 32)
• Consequence: PPP1R12B NM_002481.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.186
• 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=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0937 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.2491-15929A>G		intron	N/A	NP_002472.2
	PPP1R12B	NM_001331029.2		c.2674-15929A>G		intron	N/A	NP_001317958.1
	PPP1R12B	NM_001410283.1		c.2491-15929A>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.2491-15929A>G		intron	N/A	ENSP00000476755.1
	PPP1R12B	ENST00000290419.9	TSL:1	c.169-15929A>G		intron	N/A	ENSP00000484005.1
	PPP1R12B	ENST00000491336.5	TSL:1	c.169-15929A>G		intron	N/A	ENSP00000480852.1

Frequencies

GnomAD3 genomes AF: 0.0306 AC: 4655 AN: 152110 Hom.: 189 Cov.: 32

Gnomad AFR AF: 0.0963

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0169

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00487

Gnomad OTH AF: 0.0249

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

GnomAD4 genome AF: 0.0306 AC: 4661 AN: 152228 Hom.: 189 Cov.: 32 AF XY: 0.0291 AC XY: 2167 AN XY: 74452

African (AFR) AF: 0.0962 AC: 3994 AN: 41512

American (AMR) AF: 0.0168 AC: 257 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4828

European-Finnish (FIN) AF: 0.00151 AC: 16 AN: 10616

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00487 AC: 331 AN: 68006

Other (OTH) AF: 0.0246 AC: 52 AN: 2110

Alfa AF: 0.0213 Hom.: 22

Bravo AF: 0.0340

Asia WGS AF: 0.00664 AC: 24 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.2
DANN	Benign	0.80
PhyloP100		0.19
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: rs697455; hg19: chr1-202512076;