chr12-79668450-A-C

Variant names:

• chr12-79668450-A-C
• rs7297018
• NM_002583.4:c.516+21279T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002583.4(PAWR):​c.516+21279T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: PAWR NM_002583.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0290
• Publications: 11 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002583.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAWR	NM_002583.4	MANE Select	c.516+21279T>G		intron	N/A	NP_002574.2
	PAWR	NM_001354732.2		c.516+21279T>G		intron	N/A	NP_001341661.1
	PAWR	NM_001354733.2		c.516+21279T>G		intron	N/A	NP_001341662.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAWR	ENST00000328827.9	TSL:1 MANE Select	c.516+21279T>G		intron	N/A	ENSP00000328088.4
	PAWR	ENST00000551712.1	TSL:3	c.351+21279T>G		intron	N/A	ENSP00000448317.1
	PAWR	ENST00000547571.1	TSL:3	n.303-42T>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.1
DANN	Benign	0.77
PhyloP100		-0.029

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7297018; hg19: chr12-80062230;