rs6095228

Positions:

• chr20-48663338-G-A

Variant summary

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

The NM_020820.4(PREX1):​c.1738+2945C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0652 in 152,278 control chromosomes in the GnomAD database, including 380 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 0.065 (380 hom., cov: 32)
• Consequence: PREX1 NM_020820.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.115

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 = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PREX1	NM_020820.4	c.1738+2945C>T		intron_variant		ENST00000371941.4	NP_065871.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PREX1	ENST00000371941.4	c.1738+2945C>T		intron_variant		1	NM_020820.4	ENSP00000361009.3

Frequencies

GnomAD3 genomes AF: 0.0651 AC: 9913 AN: 152160 Hom.: 381 Cov.: 32

Gnomad AFR AF: 0.0353

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0986

Gnomad ASJ AF: 0.0942

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.0467

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0678

Gnomad OTH AF: 0.0780

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

GnomAD4 genome AF: 0.0652 AC: 9923 AN: 152278 Hom.: 380 Cov.: 32 AF XY: 0.0666 AC XY: 4961 AN XY: 74452

Gnomad4 AFR AF: 0.0354

Gnomad4 AMR AF: 0.0988

Gnomad4 ASJ AF: 0.0942

Gnomad4 EAS AF: 0.127

Gnomad4 SAS AF: 0.131

Gnomad4 FIN AF: 0.0467

Gnomad4 NFE AF: 0.0677

Gnomad4 OTH AF: 0.0767

Alfa AF: 0.0689 Hom.: 55

Bravo AF: 0.0665

Asia WGS AF: 0.104 AC: 360 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	3.9
DANN	Benign	0.51

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: rs6095228; hg19: chr20-47279876; COSMIC: COSV64258682;