chr22-44718042-A-G

Variant names:

• chr22-44718042-A-G
• rs6007260
• NM_181333.4:c.215+3371A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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:34512): (PRR5-ARHGAP8 readthrough) The PRR5-ARHGAP8 mRNA is an infrequent but naturally occurring read-through transcript of the neighboring proline rich 5, renal (PRR5) and Rho GTPase activating protein 8 (ARHGAP8) genes. The resulting fusion protein contains sequence identity with each individual gene product, and it includes domains characteristic of a RhoGAP protein. The significance of this read-through transcript and the function of its protein product have not yet been determined. [provided by RefSeq, Nov 2010]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181333.4. 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
	PRR5	NM_181333.4	MANE Select	c.215+3371A>G		intron	N/A	NP_851850.1
	PRR5-ARHGAP8	NM_181334.6		c.215+3371A>G		intron	N/A	NP_851851.3
	PRR5	NM_001198721.2		c.284+3371A>G		intron	N/A	NP_001185650.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRR5	ENST00000336985.11	TSL:1 MANE Select	c.215+3371A>G		intron	N/A	ENSP00000337464.6
	PRR5-ARHGAP8	ENST00000352766.11	TSL:2	c.215+3371A>G		intron	N/A	ENSP00000262731.11
	PRR5-ARHGAP8	ENST00000361473.9	TSL:5	c.215+3371A>G		intron	N/A	ENSP00000354732.5

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

African (AFR) AF: 0.345 AC: 14303 AN: 41416

American (AMR) AF: 0.441 AC: 6722 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 1472 AN: 3470

East Asian (EAS) AF: 0.337 AC: 1730 AN: 5132

South Asian (SAS) AF: 0.562 AC: 2703 AN: 4812

European-Finnish (FIN) AF: 0.322 AC: 3387 AN: 10532

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.334 AC: 22720 AN: 67932

Other (OTH) AF: 0.354 AC: 747 AN: 2112

Alfa AF: 0.347 Hom.: 23447

Bravo AF: 0.359

Asia WGS AF: 0.441 AC: 1535 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.6
DANN	Benign	0.11
PhyloP100		-1.3
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: rs6007260; hg19: chr22-45113922;