rs4803817

Positions:

• chr19-45404702-A-G

Variant summary

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

The NM_006663.4(PPP1R13L):​c.-22+297T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 151,936 control chromosomes in the GnomAD database, including 6,440 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 0.28 (6440 hom., cov: 31)
• Consequence: PPP1R13L NM_006663.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.164

Genes affected

PPP1R13L (HGNC:18838): (protein phosphatase 1 regulatory subunit 13 like) IASPP is one of the most evolutionarily conserved inhibitors of p53 (TP53; MIM 191170), whereas ASPP1 (MIM 606455) and ASPP2 (MIM 602143) are activators of p53.[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP1R13L	NM_006663.4	c.-22+297T>C		intron_variant		ENST00000360957.10	NP_006654.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP1R13L	ENST00000360957.10	c.-22+297T>C		intron_variant		1	NM_006663.4	ENSP00000354218	P1

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42566 AN: 151816 Hom.: 6421 Cov.: 31

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.271

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

GnomAD4 genome AF: 0.281 AC: 42634 AN: 151936 Hom.: 6440 Cov.: 31 AF XY: 0.280 AC XY: 20826 AN XY: 74292

Gnomad4 AFR AF: 0.373

Gnomad4 AMR AF: 0.354

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.311

Gnomad4 SAS AF: 0.304

Gnomad4 FIN AF: 0.172

Gnomad4 NFE AF: 0.224

Gnomad4 OTH AF: 0.276

Alfa AF: 0.242 Hom.: 6630

Bravo AF: 0.300

Asia WGS AF: 0.328 AC: 1141 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.9
DANN	Benign	0.76

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: rs4803817; hg19: chr19-45907960;