rs4476703

Variant names:

• chr5-156852464-T-C
• rs4476703
• NM_206858.3:c.*1284T>C

Variant summary

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

The NM_206858.3(PPP1R2B):​c.*1284T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0923 in 152,114 control chromosomes in the GnomAD database, including 693 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 0.092 (693 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PPP1R2B NM_206858.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.574
• Publications: 3 publications found

Genes affected

PPP1R2B (HGNC:16318): (PPP1R2 family member B) Predicted to enable protein phosphatase inhibitor activity. Predicted to be involved in regulation of phosphoprotein phosphatase activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R2B	NM_206858.3	c.*1284T>C		3_prime_UTR_variant	Exon 1 of 1	ENST00000522232.3	NP_996740.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1R2B	ENST00000522232.3	c.*1284T>C		3_prime_UTR_variant	Exon 1 of 1	6	NM_206858.3	ENSP00000490297.1

Frequencies

GnomAD3 genomes AF: 0.0921 AC: 13993 AN: 151996 Hom.: 688 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.0859

Gnomad ASJ AF: 0.0625

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.0978

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0711

Gnomad OTH AF: 0.0747

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0923 AC: 14045 AN: 152114 Hom.: 693 Cov.: 32 AF XY: 0.0940 AC XY: 6991 AN XY: 74346

African (AFR) AF: 0.122 AC: 5070 AN: 41522

American (AMR) AF: 0.0867 AC: 1325 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0625 AC: 217 AN: 3470

East Asian (EAS) AF: 0.110 AC: 567 AN: 5174

South Asian (SAS) AF: 0.143 AC: 690 AN: 4818

European-Finnish (FIN) AF: 0.0978 AC: 1035 AN: 10580

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0711 AC: 4829 AN: 67954

Other (OTH) AF: 0.0735 AC: 155 AN: 2110

Alfa AF: 0.0828 Hom.: 117

Bravo AF: 0.0919

Asia WGS AF: 0.123 AC: 426 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	10
DANN	Benign	0.72
PhyloP100		0.57

Splicing

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

Other links and lift over

dbSNP: rs4476703; hg19: chr5-156279475;