12-79650387-C-T

Position:

• chr12-79650387-C-T

Variant summary

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

The NM_002583.4(PAWR):​c.517-29180G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 152,024 control chromosomes in the GnomAD database, including 23,868 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 0.50 (23868 hom., cov: 31)
• Consequence: PAWR NM_002583.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.464

Genes affected

PAWR (HGNC:8614): (pro-apoptotic WT1 regulator) This gene encodes a tumor suppressor protein that selectively induces apoptosis in cancer cells through intracellular and extracellular mechanisms. The intracellular mechanism involves the inhibition of pro-survival pathways and the activation of Fas-mediated apoptosis, while the extracellular mechanism involves the binding of a secreted form of this protein to glucose regulated protein 78 (GRP78) on the cell surface, which leads to activation of the extrinsic apoptotic pathway. This gene is located on the unstable human chromosomal 12q21 region and is often deleted or mutated different tumors. The encoded protein also plays an important role in the progression of age-related diseases. [provided by RefSeq, Aug 2017]

PAWR (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAWR	NM_002583.4	c.517-29180G>A		intron_variant		ENST00000328827.9	NP_002574.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAWR	ENST00000328827.9	c.517-29180G>A		intron_variant		1	NM_002583.4	ENSP00000328088.4
PAWR	ENST00000551712.1	c.352-29180G>A		intron_variant		3		ENSP00000448317.1
PAWR	ENST00000550006.1	n.330-14767G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76399 AN: 151908 Hom.: 23875 Cov.: 31

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.660

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.741

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.681

Gnomad OTH AF: 0.519

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

GnomAD4 genome AF: 0.502 AC: 76385 AN: 152024 Hom.: 23868 Cov.: 31 AF XY: 0.506 AC XY: 37568 AN XY: 74308

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.599

Gnomad4 ASJ AF: 0.487

Gnomad4 EAS AF: 0.415

Gnomad4 SAS AF: 0.470

Gnomad4 FIN AF: 0.741

Gnomad4 NFE AF: 0.681

Gnomad4 OTH AF: 0.513

Alfa AF: 0.573 Hom.: 4227

Bravo AF: 0.475

Asia WGS AF: 0.389 AC: 1353 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.41

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: rs4842318; hg19: chr12-80044167;