rs1970764

Variant names:

• chr19-45387615-T-C
• rs1970764
• NM_006663.4:c.1816-1435A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 publications found

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]

PPP1R13L Gene-Disease associations (from GenCC):

• arrhythmogenic cardiomyopathy with variable ectodermal abnormalities

  Inheritance: AR Classification: DEFINITIVE Submitted by: Ambry Genetics
• dilated cardiomyopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PPP1R13L	NM_006663.4	c.1816-1435A>G		intron_variant	Intron 8 of 12	ENST00000360957.10	NP_006654.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1R13L	ENST00000360957.10	c.1816-1435A>G		intron_variant	Intron 8 of 12	1	NM_006663.4	ENSP00000354218.4
PPP1R13L	ENST00000418234.6	c.1816-1435A>G		intron_variant	Intron 8 of 12	1		ENSP00000403902.1
PPP1R13L	ENST00000587270.5	n.1289-1435A>G		intron_variant	Intron 1 of 5	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

African (AFR) AF: 0.388 AC: 16060 AN: 41432

American (AMR) AF: 0.295 AC: 4501 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 887 AN: 3468

East Asian (EAS) AF: 0.462 AC: 2357 AN: 5106

South Asian (SAS) AF: 0.281 AC: 1351 AN: 4812

European-Finnish (FIN) AF: 0.197 AC: 2082 AN: 10554

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 14015 AN: 67934

Other (OTH) AF: 0.279 AC: 588 AN: 2106

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
PhyloP100		-2.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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