1-202459732-T-C

Variant names:

• chr1-202459732-T-C
• rs805909
• NM_002481.4:c.1850+10561T>C

Variant summary

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

The NM_002481.4(PPP1R12B):​c.1850+10561T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.855 in 152,178 control chromosomes in the GnomAD database, including 55,629 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 0.85 (55629 hom., cov: 31)
• Consequence: PPP1R12B NM_002481.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.744
• Publications: 3 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.872 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R12B	NM_002481.4	c.1850+10561T>C		intron_variant	Intron 13 of 23	ENST00000608999.6	NP_002472.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1R12B	ENST00000608999.6	c.1850+10561T>C		intron_variant	Intron 13 of 23	1	NM_002481.4	ENSP00000476755.1
PPP1R12B	ENST00000391959.5	c.2033+10561T>C		intron_variant	Intron 14 of 24	5		ENSP00000375821.5
PPP1R12B	ENST00000704899.1	c.1850+10561T>C		intron_variant	Intron 13 of 23			ENSP00000516058.1
PPP1R12B	ENST00000498070.5	n.490+10561T>C		intron_variant	Intron 2 of 7	5

Frequencies

GnomAD3 genomes AF: 0.855 AC: 129970 AN: 152060 Hom.: 55586 Cov.: 31

Gnomad AFR AF: 0.816

Gnomad AMI AF: 0.814

Gnomad AMR AF: 0.884

Gnomad ASJ AF: 0.868

Gnomad EAS AF: 0.877

Gnomad SAS AF: 0.831

Gnomad FIN AF: 0.873

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.869

Gnomad OTH AF: 0.844

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

GnomAD4 genome AF: 0.855 AC: 130070 AN: 152178 Hom.: 55629 Cov.: 31 AF XY: 0.852 AC XY: 63392 AN XY: 74392

African (AFR) AF: 0.816 AC: 33887 AN: 41504

American (AMR) AF: 0.884 AC: 13518 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.868 AC: 3007 AN: 3466

East Asian (EAS) AF: 0.876 AC: 4540 AN: 5180

South Asian (SAS) AF: 0.831 AC: 4005 AN: 4818

European-Finnish (FIN) AF: 0.873 AC: 9246 AN: 10586

Middle Eastern (MID) AF: 0.755 AC: 222 AN: 294

European-Non Finnish (NFE) AF: 0.869 AC: 59119 AN: 68026

Other (OTH) AF: 0.846 AC: 1784 AN: 2108

Alfa AF: 0.863 Hom.: 10815

Bravo AF: 0.853

Asia WGS AF: 0.839 AC: 2920 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.2
DANN	Benign	0.65
PhyloP100		-0.74
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: rs805909; hg19: chr1-202428860;