2-28751664-A-C

Variant names:

• chr2-28751664-A-C
• rs147139861
• NM_206876.2:c.-244A>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_206876.2(PPP1CB):​c.-244A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0123 in 184,138 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (47 hom., cov: 31)
  • Exomes 𝑓: 0.0031 (0 hom.)
• Consequence: PPP1CB NM_206876.2 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.84

Genes affected

PPP1CB (HGNC:9282): (protein phosphatase 1 catalytic subunit beta) The protein encoded by this gene is one of the three catalytic subunits of protein phosphatase 1 (PP1). PP1 is a serine/threonine specific protein phosphatase known to be involved in the regulation of a variety of cellular processes, such as cell division, glycogen metabolism, muscle contractility, protein synthesis, and HIV-1 viral transcription. Mouse studies suggest that PP1 functions as a suppressor of learning and memory. Two alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]

PPP1CB-DT (HGNC:55829): (PPP1CB divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 2-28751664-A-C is Benign according to our data. Variant chr2-28751664-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 1191835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0142 (2169/152302) while in subpopulation AFR AF = 0.0403 (1675/41580). AF 95% confidence interval is 0.0387. There are 47 homozygotes in GnomAd4. There are 1098 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2169 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1CB	NM_002709.3	c.-461A>C		upstream_gene_variant		ENST00000395366.3	NP_002700.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1CB	ENST00000395366.3	c.-461A>C		upstream_gene_variant		1	NM_002709.3	ENSP00000378769.2

Frequencies

GnomAD3 genomes AF: 0.0143 AC: 2171 AN: 152194 Hom.: 47 Cov.: 31

Gnomad AFR AF: 0.0404

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00497

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00393

Gnomad FIN AF: 0.0197

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00231

Gnomad OTH AF: 0.00622

GnomAD4 exome AF: 0.00308 AC: 98 AN: 31836 Hom.: 0 Cov.: 0 AF XY: 0.00223 AC XY: 40 AN XY: 17920

African (AFR) AF: 0.0469 AC: 9 AN: 192

American (AMR) AF: 0.00 AC: 0 AN: 126

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 624

East Asian (EAS) AF: 0.00 AC: 0 AN: 184

South Asian (SAS) AF: 0.00148 AC: 11 AN: 7414

European-Finnish (FIN) AF: 0.0104 AC: 20 AN: 1914

Middle Eastern (MID) AF: 0.0111 AC: 1 AN: 90

European-Non Finnish (NFE) AF: 0.00224 AC: 44 AN: 19642

Other (OTH) AF: 0.00788 AC: 13 AN: 1650

GnomAD4 genome AF: 0.0142 AC: 2169 AN: 152302 Hom.: 47 Cov.: 31 AF XY: 0.0147 AC XY: 1098 AN XY: 74476

African (AFR) AF: 0.0403 AC: 1675 AN: 41580

American (AMR) AF: 0.00490 AC: 75 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00576 AC: 20 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5170

South Asian (SAS) AF: 0.00373 AC: 18 AN: 4832

European-Finnish (FIN) AF: 0.0197 AC: 209 AN: 10616

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.00231 AC: 157 AN: 68012

Other (OTH) AF: 0.00616 AC: 13 AN: 2112

Alfa AF: 0.00145 Hom.: 0

Bravo AF: 0.0152

Asia WGS AF: 0.00579 AC: 20 AN: 3470

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 21, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.052
DANN	Benign	0.52
PhyloP100		-2.8
PromoterAI		0.034	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Other links and lift over

dbSNP: rs147139861; hg19: chr2-28974530;