rs1970764

Positions:

• chr19-45387615-T-C

Variant summary

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

The NM_006663.4(PPP1R13L):​c.1816-1435A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 151,870 control chromosomes in the GnomAD database, including 6,461 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 (6461 hom., cov: 30)
• Consequence: PPP1R13L NM_006663.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.46

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=-1.06).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP1R13L	NM_006663.4	c.1816-1435A>G		intron_variant		ENST00000360957.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP1R13L	ENST00000360957.10	c.1816-1435A>G		intron_variant		1	NM_006663.4	P1
PPP1R13L	ENST00000418234.6	c.1816-1435A>G		intron_variant		1		P1
PPP1R13L	ENST00000587270.5	n.1289-1435A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41899 AN: 151752 Hom.: 6428 Cov.: 30

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.275

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

GnomAD4 genome AF: 0.276 AC: 41985 AN: 151870 Hom.: 6461 Cov.: 30 AF XY: 0.276 AC XY: 20488 AN XY: 74206

Gnomad4 AFR AF: 0.388

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.256

Gnomad4 EAS AF: 0.462

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.279

Alfa AF: 0.241 Hom.: 614

Bravo AF: 0.293

Asia WGS AF: 0.378 AC: 1313 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.52
DANN	Benign	0.24

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: rs1970764; hg19: chr19-45890873; COSMIC: COSV62908729; COSMIC: COSV62908729;