1-202447994-A-G

Variant names:

• chr1-202447994-A-G
• rs3767424
• NM_002481.4:c.1668-995A>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.1668-995A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0209 in 151,302 control chromosomes in the GnomAD database, including 245 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 0.021 (245 hom., cov: 32)
• Consequence: PPP1R12B NM_002481.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.853
• Publications: 1 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]

ENSG00000297456 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R12B	NM_002481.4	c.1668-995A>G		intron_variant	Intron 12 of 23	ENST00000608999.6	NP_002472.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1R12B	ENST00000608999.6	c.1668-995A>G		intron_variant	Intron 12 of 23	1	NM_002481.4	ENSP00000476755.1

Frequencies

GnomAD3 genomes AF: 0.0209 AC: 3159 AN: 151186 Hom.: 244 Cov.: 32

Gnomad AFR AF: 0.00316

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0775

Gnomad ASJ AF: 0.000578

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.0184

Gnomad FIN AF: 0.0255

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00217

Gnomad OTH AF: 0.0226

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

GnomAD4 genome AF: 0.0209 AC: 3162 AN: 151302 Hom.: 245 Cov.: 32 AF XY: 0.0248 AC XY: 1834 AN XY: 73882

African (AFR) AF: 0.00316 AC: 130 AN: 41198

American (AMR) AF: 0.0777 AC: 1181 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.000578 AC: 2 AN: 3462

East Asian (EAS) AF: 0.252 AC: 1300 AN: 5158

South Asian (SAS) AF: 0.0184 AC: 88 AN: 4788

European-Finnish (FIN) AF: 0.0255 AC: 267 AN: 10452

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00217 AC: 147 AN: 67734

Other (OTH) AF: 0.0223 AC: 47 AN: 2104

Alfa AF: 0.0107 Hom.: 9

Bravo AF: 0.0245

Asia WGS AF: 0.100 AC: 347 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.053
DANN	Benign	0.72
PhyloP100		-0.85
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: rs3767424; hg19: chr1-202417122;