rs6007260

chr22-44718042-A-G

Variant summary

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

The NM_181333.4(PRR5):c.215+3371A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 151,862 control chromosomes in the GnomAD database, including 9,880 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 (9880 hom., cov: 31)
• Consequence: PRR5 NM_181333.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34

Genes affected

PRR5 (HGNC:31682): (proline rich 5) This gene encodes a protein with a proline-rich domain. This gene is located in a region of chromosome 22 reported to contain a tumor suppressor gene that may be involved in breast and colorectal tumorigenesis. The protein is a component of the mammalian target of rapamycin complex 2 (mTORC2), and it regulates platelet-derived growth factor (PDGF) receptor beta expression and PDGF signaling to Akt and S6K1. Alternative splicing and the use of alternative promoters results in transcripts encoding different isoforms. Read-through transcripts from this gene into the downstream Rho GTPase activating protein 8 (ARHGAP8) gene also exist, which led to the original description of PRR5 and ARHGAP8 being a single gene. [provided by RefSeq, Nov 2010]

PRR5-ARHGAP8 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRR5	NM_181333.4	c.215+3371A>G		intron_variant		ENST00000336985.11
PRR5-ARHGAP8	NM_181334.6	c.215+3371A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRR5	ENST00000336985.11	c.215+3371A>G		intron_variant		1	NM_181333.4	P4

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53945 AN: 151744 Hom.: 9859 Cov.: 31

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.352

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

GnomAD4 genome AF: 0.356 AC: 54010 AN: 151862 Hom.: 9880 Cov.: 31 AF XY: 0.363 AC XY: 26933 AN XY: 74218

Gnomad4 AFR AF: 0.345

Gnomad4 AMR AF: 0.441

Gnomad4 ASJ AF: 0.424

Gnomad4 EAS AF: 0.337

Gnomad4 SAS AF: 0.562

Gnomad4 FIN AF: 0.322

Gnomad4 NFE AF: 0.334

Gnomad4 OTH AF: 0.354

Alfa AF: 0.346 Hom.: 14753

Bravo AF: 0.359

Asia WGS AF: 0.441 AC: 1535 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.6
Dann	Benign	0.11

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: rs6007260; hg19: chr22-45113922;