12-79668450-A-G

Variant names:

• chr12-79668450-A-G
• rs7297018
• NM_002583.4:c.516+21279T>C

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+21279T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.872 in 152,210 control chromosomes in the GnomAD database, including 58,159 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 0.87 (58155 hom., cov: 32)
  • Exomes 𝑓: 0.83 (4 hom.)
• Consequence: PAWR NM_002583.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0290
• Publications: 11 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.959 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+21279T>C		intron	N/A	NP_002574.2
	PAWR	NM_001354732.2		c.516+21279T>C		intron	N/A	NP_001341661.1
	PAWR	NM_001354733.2		c.516+21279T>C		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+21279T>C		intron	N/A	ENSP00000328088.4
	PAWR	ENST00000551712.1	TSL:3	c.351+21279T>C		intron	N/A	ENSP00000448317.1
	PAWR	ENST00000547571.1	TSL:3	n.303-42T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.872 AC: 132542 AN: 152080 Hom.: 58088 Cov.: 32

Gnomad AFR AF: 0.967

Gnomad AMI AF: 0.856

Gnomad AMR AF: 0.877

Gnomad ASJ AF: 0.763

Gnomad EAS AF: 0.907

Gnomad SAS AF: 0.855

Gnomad FIN AF: 0.825

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.825

Gnomad OTH AF: 0.853

GnomAD4 exome AF: 0.833 AC: 10 AN: 12 Hom.: 4 Cov.: 0 AF XY: 0.833 AC XY: 5 AN XY: 6

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AF: 1.00 AC: 2 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.750 AC: 6 AN: 8

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.872 AC: 132670 AN: 152198 Hom.: 58155 Cov.: 32 AF XY: 0.871 AC XY: 64783 AN XY: 74400

African (AFR) AF: 0.967 AC: 40186 AN: 41550

American (AMR) AF: 0.877 AC: 13410 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.763 AC: 2645 AN: 3468

East Asian (EAS) AF: 0.907 AC: 4680 AN: 5160

South Asian (SAS) AF: 0.855 AC: 4123 AN: 4820

European-Finnish (FIN) AF: 0.825 AC: 8729 AN: 10582

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.825 AC: 56104 AN: 68008

Other (OTH) AF: 0.854 AC: 1804 AN: 2112

Alfa AF: 0.839 Hom.: 116964

Bravo AF: 0.878

Asia WGS AF: 0.876 AC: 3046 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.2
DANN	Benign	0.80
PhyloP100		-0.029
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7297018; hg19: chr12-80062230;