20-48653064-C-G

Position:

• chr20-48653064-C-G

Variant summary

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

The NM_020820.4(PREX1):​c.2346+297G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,130 control chromosomes in the GnomAD database, including 2,806 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 0.19 (2806 hom., cov: 32)
• Consequence: PREX1 NM_020820.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43

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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PREX1	NM_020820.4	c.2346+297G>C		intron_variant		ENST00000371941.4	NP_065871.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PREX1	ENST00000371941.4	c.2346+297G>C		intron_variant		1	NM_020820.4	ENSP00000361009	P1
PREX1	ENST00000482556.5	c.311+297G>C		intron_variant, NMD_transcript_variant		2		ENSP00000434632

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28951 AN: 152012 Hom.: 2796 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.210

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.191 AC: 28994 AN: 152130 Hom.: 2806 Cov.: 32 AF XY: 0.191 AC XY: 14173 AN XY: 74388

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.233

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.207

Gnomad4 SAS AF: 0.287

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.194

Gnomad4 OTH AF: 0.225

Alfa AF: 0.0914 Hom.: 109

Bravo AF: 0.191

Asia WGS AF: 0.257 AC: 894 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.050
DANN	Benign	0.40

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: rs2073072; hg19: chr20-47269602;