chr22-44719699-A-G

Variant names:

• chr22-44719699-A-G
• rs5765930
• NM_181333.4:c.215+5028A>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+5028A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.829 in 152,116 control chromosomes in the GnomAD database, including 52,349 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 0.83 (52349 hom., cov: 32)
• Consequence: PRR5 NM_181333.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.96
• 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=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRR5	NM_181333.4	c.215+5028A>G		intron_variant	Intron 2 of 7	ENST00000336985.11	NP_851850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRR5	ENST00000336985.11	c.215+5028A>G		intron_variant	Intron 2 of 7	1	NM_181333.4	ENSP00000337464.6
PRR5-ARHGAP8	ENST00000352766.11	c.215+5028A>G		intron_variant	Intron 2 of 16	2		ENSP00000262731.11

Frequencies

GnomAD3 genomes AF: 0.829 AC: 126028 AN: 151998 Hom.: 52303 Cov.: 32

Gnomad AFR AF: 0.830

Gnomad AMI AF: 0.843

Gnomad AMR AF: 0.808

Gnomad ASJ AF: 0.819

Gnomad EAS AF: 0.891

Gnomad SAS AF: 0.880

Gnomad FIN AF: 0.788

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.832

Gnomad OTH AF: 0.810

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

GnomAD4 genome AF: 0.829 AC: 126125 AN: 152116 Hom.: 52349 Cov.: 32 AF XY: 0.831 AC XY: 61746 AN XY: 74340

African (AFR) AF: 0.831 AC: 34467 AN: 41500

American (AMR) AF: 0.808 AC: 12347 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.819 AC: 2841 AN: 3468

East Asian (EAS) AF: 0.890 AC: 4585 AN: 5150

South Asian (SAS) AF: 0.879 AC: 4230 AN: 4812

European-Finnish (FIN) AF: 0.788 AC: 8345 AN: 10592

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.832 AC: 56586 AN: 67998

Other (OTH) AF: 0.809 AC: 1706 AN: 2110

Alfa AF: 0.832 Hom.: 225287

Bravo AF: 0.829

Asia WGS AF: 0.846 AC: 2943 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	1.3
DANN	Benign	0.27
PhyloP100		-4.0
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: rs5765930; hg19: chr22-45115579;