chr12-79661347-T-C

Variant names:

• chr12-79661347-T-C
• rs17005769
• NM_002583.4:c.516+28382A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002583.4(PAWR):​c.516+28382A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.032 in 152,062 control chromosomes in the GnomAD database, including 237 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 0.032 (237 hom., cov: 32)
• Consequence: PAWR NM_002583.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.506
• Publications: 5 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 (SAS) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAWR	NM_002583.4	c.516+28382A>G		intron_variant	Intron 2 of 6	ENST00000328827.9	NP_002574.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAWR	ENST00000328827.9	c.516+28382A>G		intron_variant	Intron 2 of 6	1	NM_002583.4	ENSP00000328088.4
PAWR	ENST00000551712.1	c.351+28382A>G		intron_variant	Intron 1 of 3	3		ENSP00000448317.1
PAWR	ENST00000550006.1	n.330-25727A>G		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.0319 AC: 4843 AN: 151948 Hom.: 235 Cov.: 32

Gnomad AFR AF: 0.00587

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0436

Gnomad ASJ AF: 0.0282

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.0308

Gnomad MID AF: 0.0769

Gnomad NFE AF: 0.0227

Gnomad OTH AF: 0.0307

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

GnomAD4 genome AF: 0.0320 AC: 4866 AN: 152062 Hom.: 237 Cov.: 32 AF XY: 0.0364 AC XY: 2707 AN XY: 74330

African (AFR) AF: 0.00585 AC: 243 AN: 41506

American (AMR) AF: 0.0443 AC: 676 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0282 AC: 98 AN: 3472

East Asian (EAS) AF: 0.183 AC: 949 AN: 5174

South Asian (SAS) AF: 0.186 AC: 898 AN: 4818

European-Finnish (FIN) AF: 0.0308 AC: 325 AN: 10536

Middle Eastern (MID) AF: 0.0793 AC: 23 AN: 290

European-Non Finnish (NFE) AF: 0.0227 AC: 1541 AN: 67978

Other (OTH) AF: 0.0360 AC: 76 AN: 2110

Alfa AF: 0.0232 Hom.: 20

Bravo AF: 0.0292

Asia WGS AF: 0.185 AC: 643 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.0
DANN	Benign	0.66
PhyloP100		-0.51
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: rs17005769; hg19: chr12-80055127;