12-79668450-A-G

Position:

• chr12-79668450-A-G

Variant summary

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

The NM_002583.4(PAWR):​c.516+21279T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.872 in 152,210 control chromosomes in the GnomAD database, including 58,159 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 0.87 (58155 hom., cov: 32)
  • Exomes 𝑓: 0.83 (4 hom.)
• Consequence: PAWR NM_002583.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0290

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.959 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAWR	NM_002583.4	c.516+21279T>C		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+21279T>C		intron_variant		1	NM_002583.4	ENSP00000328088	P1
PAWR	ENST00000551712.1	c.352+21279T>C		intron_variant		3		ENSP00000448317
PAWR	ENST00000547571.1	n.303-42T>C		intron_variant, non_coding_transcript_variant		3
PAWR	ENST00000550006.1	n.329+21279T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.872 AC: 132542 AN: 152080 Hom.: 58088 Cov.: 32

Gnomad AFR AF: 0.967

Gnomad AMI AF: 0.856

Gnomad AMR AF: 0.877

Gnomad ASJ AF: 0.763

Gnomad EAS AF: 0.907

Gnomad SAS AF: 0.855

Gnomad FIN AF: 0.825

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.825

Gnomad OTH AF: 0.853

GnomAD4 exome AF: 0.833 AC: 10 AN: 12 Hom.: 4 Cov.: 0 AF XY: 0.833 AC XY: 5 AN XY: 6

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 1.00

Gnomad4 NFE exome AF: 0.750

GnomAD4 genome AF: 0.872 AC: 132670 AN: 152198 Hom.: 58155 Cov.: 32 AF XY: 0.871 AC XY: 64783 AN XY: 74400

Gnomad4 AFR AF: 0.967

Gnomad4 AMR AF: 0.877

Gnomad4 ASJ AF: 0.763

Gnomad4 EAS AF: 0.907

Gnomad4 SAS AF: 0.855

Gnomad4 FIN AF: 0.825

Gnomad4 NFE AF: 0.825

Gnomad4 OTH AF: 0.854

Alfa AF: 0.829 Hom.: 76968

Bravo AF: 0.878

Asia WGS AF: 0.876 AC: 3046 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.2
DANN	Benign	0.80

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

Publications

LitVar

Other links and lift over

dbSNP: rs7297018; hg19: chr12-80062230;