chr12-79685268-G-A

Position:

• chr12-79685268-G-A

Variant summary

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

The NM_002583.4(PAWR):​c.516+4461C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 151,942 control chromosomes in the GnomAD database, including 16,530 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 0.36 (16530 hom., cov: 31)
• Consequence: PAWR NM_002583.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.445

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=-0.58).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAWR	NM_002583.4	c.516+4461C>T		intron_variant		ENST00000328827.9	NP_002574.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAWR	ENST00000328827.9	c.516+4461C>T		intron_variant		1	NM_002583.4	ENSP00000328088.4
PAWR	ENST00000551712.1	c.351+4461C>T		intron_variant		3		ENSP00000448317.1
PAWR	ENST00000547571.1	n.302+4461C>T		intron_variant		3
PAWR	ENST00000550006.1	n.329+4461C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54125 AN: 151824 Hom.: 16474 Cov.: 31

Gnomad AFR AF: 0.834

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.0941

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.320

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

GnomAD4 genome AF: 0.357 AC: 54239 AN: 151942 Hom.: 16530 Cov.: 31 AF XY: 0.349 AC XY: 25904 AN XY: 74244

Gnomad4 AFR AF: 0.834

Gnomad4 AMR AF: 0.253

Gnomad4 ASJ AF: 0.259

Gnomad4 EAS AF: 0.300

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.0941

Gnomad4 NFE AF: 0.154

Gnomad4 OTH AF: 0.322

Alfa AF: 0.206 Hom.: 2549

Bravo AF: 0.391

Asia WGS AF: 0.292 AC: 1015 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	1.1
DANN	Benign	0.85

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: rs2463169; hg19: chr12-80079048;