rs6696611

Variant names:

• chr1-202524561-G-T
• rs6696611
• NM_002481.4:c.2490+27739G>T

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+27739G>T 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 151,944 control chromosomes in the GnomAD database, including 15,683 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 (15683 hom., cov: 31)
• Consequence: PPP1R12B NM_002481.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.926
• 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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.687 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R12B	NM_002481.4	MANE Select	c.2490+27739G>T		intron	N/A	NP_002472.2	O60237-1
	PPP1R12B	NM_001331029.2		c.2673+27739G>T		intron	N/A	NP_001317958.1	O60237-6
	PPP1R12B	NM_001410283.1		c.2490+27739G>T		intron	N/A	NP_001397212.1	A0A994J7P4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R12B	ENST00000608999.6	TSL:1 MANE Select	c.2490+27739G>T		intron	N/A	ENSP00000476755.1	O60237-1
	PPP1R12B	ENST00000290419.9	TSL:1	c.168+27739G>T		intron	N/A	ENSP00000484005.1	O60237-3
	PPP1R12B	ENST00000491336.5	TSL:1	c.168+27739G>T		intron	N/A	ENSP00000480852.1	O60237-4

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65967 AN: 151826 Hom.: 15674 Cov.: 31

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.707

Gnomad SAS AF: 0.629

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.478

Gnomad OTH AF: 0.422

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

GnomAD4 genome AF: 0.434 AC: 65992 AN: 151944 Hom.: 15683 Cov.: 31 AF XY: 0.439 AC XY: 32583 AN XY: 74252

African (AFR) AF: 0.255 AC: 10544 AN: 41430

American (AMR) AF: 0.578 AC: 8821 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 1271 AN: 3470

East Asian (EAS) AF: 0.706 AC: 3651 AN: 5168

South Asian (SAS) AF: 0.628 AC: 3020 AN: 4808

European-Finnish (FIN) AF: 0.463 AC: 4873 AN: 10526

Middle Eastern (MID) AF: 0.308 AC: 90 AN: 292

European-Non Finnish (NFE) AF: 0.478 AC: 32460 AN: 67960

Other (OTH) AF: 0.426 AC: 897 AN: 2108

Alfa AF: 0.468 Hom.: 2987

Bravo AF: 0.433

Asia WGS AF: 0.629 AC: 2185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.44
PhyloP100		-0.93
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: rs6696611; hg19: chr1-202493689;