12-79650387-C-T

Variant names:

• chr12-79650387-C-T
• rs4842318
• NM_002583.4:c.517-29180G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAWR	NM_002583.4	MANE Select	c.517-29180G>A		intron	N/A	NP_002574.2	Q96IZ0
	PAWR	NM_001354732.2		c.517-29180G>A		intron	N/A	NP_001341661.1	Q96IZ0
	PAWR	NM_001354733.2		c.517-29180G>A		intron	N/A	NP_001341662.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAWR	ENST00000328827.9	TSL:1 MANE Select	c.517-29180G>A		intron	N/A	ENSP00000328088.4	Q96IZ0
	PAWR	ENST00000903360.1		c.517-29180G>A		intron	N/A	ENSP00000573419.1
	PAWR	ENST00000912080.1		c.517-29180G>A		intron	N/A	ENSP00000582139.1

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

African (AFR) AF: 0.125 AC: 5199 AN: 41466

American (AMR) AF: 0.599 AC: 9149 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 1691 AN: 3472

East Asian (EAS) AF: 0.415 AC: 2144 AN: 5172

South Asian (SAS) AF: 0.470 AC: 2253 AN: 4798

European-Finnish (FIN) AF: 0.741 AC: 7830 AN: 10568

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.681 AC: 46314 AN: 67970

Other (OTH) AF: 0.513 AC: 1080 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.41
PhyloP100		0.46
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: rs4842318; hg19: chr12-80044167;