rs3767424

Variant names:

• chr1-202447994-A-G
• rs3767424
• NM_002481.4:c.1668-995A>G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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
PPP1R12B	ENST00000391959.5	c.1851-995A>G		intron_variant	Intron 13 of 24	5		ENSP00000375821.5
PPP1R12B	ENST00000704899.1	c.1668-995A>G		intron_variant	Intron 12 of 23			ENSP00000516058.1
PPP1R12B	ENST00000434615.2	n.*209-995A>G		intron_variant	Intron 3 of 3	3		ENSP00000489025.1

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

Gnomad4 AFR AF: 0.00316

Gnomad4 AMR AF: 0.0777

Gnomad4 ASJ AF: 0.000578

Gnomad4 EAS AF: 0.252

Gnomad4 SAS AF: 0.0184

Gnomad4 FIN AF: 0.0255

Gnomad4 NFE AF: 0.00217

Gnomad4 OTH AF: 0.0223

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs3767424; hg19: chr1-202417122;