rs8548

chr14-103733243-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015316.3(PPP1R13B):c.*1911T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 574,164 control chromosomes in the GnomAD database, including 27,315 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 0.27 (6493 hom., cov: 33)
  • Exomes 𝑓: 0.30 (20822 hom.)
• Consequence: PPP1R13B NM_015316.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.589

Genes affected

PPP1R13B (HGNC:14950): (protein phosphatase 1 regulatory subunit 13B) This gene encodes a member of the ASPP (apoptosis-stimulating protein of p53) family of p53 interacting proteins. The protein contains four ankyrin repeats and an SH3 domain involved in protein-protein interactions. ASPP proteins are required for the induction of apoptosis by p53-family proteins. They promote DNA binding and transactivation of p53-family proteins on the promoters of proapoptotic genes. Expression of this gene is regulated by the E2F transcription factor. [provided by RefSeq, Jul 2008]

ZFYVE21 (HGNC:20760): (zinc finger FYVE-type containing 21) Predicted to enable metal ion binding activity. Predicted to be located in endosome and focal adhesion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP1R13B	NM_015316.3	c.*1911T>G		3_prime_UTR_variant	17/17	ENST00000202556.14
ZFYVE21	NM_024071.4	c.*225A>C		3_prime_UTR_variant	7/7	ENST00000311141.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP1R13B	ENST00000202556.14	c.*1911T>G		3_prime_UTR_variant	17/17	1	NM_015316.3	P1
ZFYVE21	ENST00000311141.7	c.*225A>C		3_prime_UTR_variant	7/7	1	NM_024071.4	P1

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41144 AN: 151072 Hom.: 6482 Cov.: 33

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.195

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.259

GnomAD4 exome AF: 0.304 AC: 128650 AN: 422972 Hom.: 20822 Cov.: 5 AF XY: 0.299 AC XY: 66064 AN XY: 220922

Gnomad4 AFR exome AF: 0.112

Gnomad4 AMR exome AF: 0.265

Gnomad4 ASJ exome AF: 0.217

Gnomad4 EAS exome AF: 0.331

Gnomad4 SAS exome AF: 0.201

Gnomad4 FIN exome AF: 0.388

Gnomad4 NFE exome AF: 0.326

Gnomad4 OTH exome AF: 0.286

GnomAD4 genome AF: 0.272 AC: 41171 AN: 151192 Hom.: 6493 Cov.: 33 AF XY: 0.272 AC XY: 20117 AN XY: 73860

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.273

Gnomad4 ASJ AF: 0.225

Gnomad4 EAS AF: 0.329

Gnomad4 SAS AF: 0.212

Gnomad4 FIN AF: 0.412

Gnomad4 NFE AF: 0.347

Gnomad4 OTH AF: 0.261

Alfa AF: 0.312 Hom.: 2470

Bravo AF: 0.252

Asia WGS AF: 0.261 AC: 907 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	3.2
Dann	Benign	0.79

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: rs8548; hg19: chr14-104199580; COSMIC: COSV52448752; COSMIC: COSV52448752;