rs2463169

Variant names:

• chr12-79685268-G-A
• rs2463169
• NM_002583.4:c.516+4461C>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.516+4461C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 151,942 control chromosomes in the GnomAD database, including 16,530 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 0.36 (16530 hom., cov: 31)
• Consequence: PAWR NM_002583.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.445
• Publications: 3 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=-0.58).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.827 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAWR	NM_002583.4	MANE Select	c.516+4461C>T		intron	N/A	NP_002574.2
	PAWR	NM_001354732.2		c.516+4461C>T		intron	N/A	NP_001341661.1
	PAWR	NM_001354733.2		c.516+4461C>T		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+4461C>T		intron	N/A	ENSP00000328088.4
	PAWR	ENST00000903360.1		c.516+4461C>T		intron	N/A	ENSP00000573419.1
	PAWR	ENST00000912080.1		c.516+4461C>T		intron	N/A	ENSP00000582139.1

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54125 AN: 151824 Hom.: 16474 Cov.: 31

Gnomad AFR AF: 0.834

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.0941

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.320

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

GnomAD4 genome AF: 0.357 AC: 54239 AN: 151942 Hom.: 16530 Cov.: 31 AF XY: 0.349 AC XY: 25904 AN XY: 74244

African (AFR) AF: 0.834 AC: 34614 AN: 41486

American (AMR) AF: 0.253 AC: 3868 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 897 AN: 3464

East Asian (EAS) AF: 0.300 AC: 1537 AN: 5130

South Asian (SAS) AF: 0.203 AC: 976 AN: 4810

European-Finnish (FIN) AF: 0.0941 AC: 992 AN: 10546

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.154 AC: 10450 AN: 67920

Other (OTH) AF: 0.322 AC: 678 AN: 2106

Alfa AF: 0.210 Hom.: 2989

Bravo AF: 0.391

Asia WGS AF: 0.292 AC: 1015 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	1.1
DANN	Benign	0.85
PhyloP100		-0.45
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: rs2463169; hg19: chr12-80079048;