rs3842842

Variant names:

• chr12-79655109-T-A
• rs3842842
• NM_002583.4:c.517-33902A>T

Variant summary

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

The NM_002583.4(PAWR):​c.517-33902A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 152,212 control chromosomes in the GnomAD database, including 10,826 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 0.23 (10826 hom., cov: 32)
• Consequence: PAWR NM_002583.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23
• Publications: 1 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAWR	NM_002583.4	c.517-33902A>T		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.517-33902A>T		intron_variant	Intron 2 of 6	1	NM_002583.4	ENSP00000328088.4
PAWR	ENST00000551712.1	c.352-33902A>T		intron_variant	Intron 1 of 3	3		ENSP00000448317.1
PAWR	ENST00000550006.1	n.330-19489A>T		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34841 AN: 152094 Hom.: 10775 Cov.: 32

Gnomad AFR AF: 0.706

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.0671

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.0911

Gnomad FIN AF: 0.0201

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0184

Gnomad OTH AF: 0.168

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

GnomAD4 genome AF: 0.230 AC: 34947 AN: 152212 Hom.: 10826 Cov.: 32 AF XY: 0.224 AC XY: 16703 AN XY: 74436

African (AFR) AF: 0.706 AC: 29299 AN: 41482

American (AMR) AF: 0.128 AC: 1958 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0671 AC: 233 AN: 3472

East Asian (EAS) AF: 0.214 AC: 1110 AN: 5176

South Asian (SAS) AF: 0.0902 AC: 435 AN: 4824

European-Finnish (FIN) AF: 0.0201 AC: 214 AN: 10626

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0184 AC: 1250 AN: 68014

Other (OTH) AF: 0.169 AC: 356 AN: 2108

Alfa AF: 0.141 Hom.: 813

Bravo AF: 0.261

Asia WGS AF: 0.204 AC: 709 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.21
DANN	Benign	0.47
PhyloP100		-1.2
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: rs3842842; hg19: chr12-80048889;