rs6063312

Positions:

• chr20-48726522-G-T

Variant summary

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

The NM_020820.4(PREX1):​c.520-131C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 658,532 control chromosomes in the GnomAD database, including 9,422 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 0.14 (1835 hom., cov: 33)
  • Exomes 𝑓: 0.16 (7587 hom.)
• Consequence: PREX1 NM_020820.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06

Genes affected

PREX1 (HGNC:32594): (phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 1) The protein encoded by this gene acts as a guanine nucleotide exchange factor for the RHO family of small GTP-binding proteins (RACs). It has been shown to bind to and activate RAC1 by exchanging bound GDP for free GTP. The encoded protein, which is found mainly in the cytoplasm, is activated by phosphatidylinositol-3,4,5-trisphosphate and the beta-gamma subunits of heterotrimeric G proteins. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PREX1	NM_020820.4	c.520-131C>A		intron_variant		ENST00000371941.4	NP_065871.3
PREX1	XM_047440331.1	c.-6-131C>A		intron_variant			XP_047296287.1
PREX1	XM_047440332.1	c.-6-131C>A		intron_variant			XP_047296288.1
PREX1	XM_047440333.1	c.-6-131C>A		intron_variant			XP_047296289.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PREX1	ENST00000371941.4	c.520-131C>A		intron_variant		1	NM_020820.4	ENSP00000361009	P1

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22024 AN: 152090 Hom.: 1831 Cov.: 33

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.0959

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.178

GnomAD4 exome AF: 0.164 AC: 82827 AN: 506324 Hom.: 7587 AF XY: 0.168 AC XY: 44507 AN XY: 265278

Gnomad4 AFR exome AF: 0.104

Gnomad4 AMR exome AF: 0.281

Gnomad4 ASJ exome AF: 0.171

Gnomad4 EAS exome AF: 0.229

Gnomad4 SAS exome AF: 0.243

Gnomad4 FIN exome AF: 0.0950

Gnomad4 NFE exome AF: 0.146

Gnomad4 OTH exome AF: 0.164

GnomAD4 genome AF: 0.145 AC: 22049 AN: 152208 Hom.: 1835 Cov.: 33 AF XY: 0.147 AC XY: 10937 AN XY: 74404

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.246

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.185

Gnomad4 SAS AF: 0.262

Gnomad4 FIN AF: 0.0959

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.180

Alfa AF: 0.152 Hom.: 3886

Bravo AF: 0.151

Asia WGS AF: 0.230 AC: 798 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.1
DANN	Benign	0.57

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: rs6063312; hg19: chr20-47343059;