rs7305141

Positions:

• chr12-79621793-G-A
• chr12-79621793-G-C
• chr12-79621793-G-T

Variant summary

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

The NM_002583.4(PAWR):​c.517-586C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.862 in 152,140 control chromosomes in the GnomAD database, including 56,995 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 0.86 (56995 hom., cov: 32)
• Consequence: PAWR NM_002583.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0500

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAWR	NM_002583.4	c.517-586C>T		intron_variant		ENST00000328827.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAWR	ENST00000328827.9	c.517-586C>T		intron_variant		1	NM_002583.4	P1
PAWR	ENST00000551712.1	c.353-586C>T		intron_variant		3
PAWR	ENST00000549050.1	n.57+10313C>T		intron_variant, non_coding_transcript_variant		5
PAWR	ENST00000550006.1	n.401-586C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.862 AC: 131023 AN: 152022 Hom.: 56948 Cov.: 32

Gnomad AFR AF: 0.968

Gnomad AMI AF: 0.840

Gnomad AMR AF: 0.855

Gnomad ASJ AF: 0.746

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.674

Gnomad FIN AF: 0.834

Gnomad MID AF: 0.638

Gnomad NFE AF: 0.835

Gnomad OTH AF: 0.842

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

GnomAD4 genome AF: 0.862 AC: 131127 AN: 152140 Hom.: 56995 Cov.: 32 AF XY: 0.857 AC XY: 63745 AN XY: 74388

Gnomad4 AFR AF: 0.968

Gnomad4 AMR AF: 0.855

Gnomad4 ASJ AF: 0.746

Gnomad4 EAS AF: 0.715

Gnomad4 SAS AF: 0.673

Gnomad4 FIN AF: 0.834

Gnomad4 NFE AF: 0.835

Gnomad4 OTH AF: 0.838

Alfa AF: 0.828 Hom.: 45577

Bravo AF: 0.869

Asia WGS AF: 0.683 AC: 2370 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.1
DANN	Benign	0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs7305141; hg19: chr12-80015573;