20-48653064-C-G

Variant names:

• chr20-48653064-C-G
• rs2073072
• NM_020820.4:c.2346+297G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PREX1	NM_020820.4	c.2346+297G>C		intron_variant	Intron 20 of 39	ENST00000371941.4	NP_065871.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PREX1	ENST00000371941.4	c.2346+297G>C		intron_variant	Intron 20 of 39	1	NM_020820.4	ENSP00000361009.3
PREX1	ENST00000482556.5	n.309+297G>C		intron_variant	Intron 3 of 21	2		ENSP00000434632.1

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

African (AFR) AF: 0.156 AC: 6476 AN: 41502

American (AMR) AF: 0.233 AC: 3565 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 827 AN: 3470

East Asian (EAS) AF: 0.207 AC: 1069 AN: 5172

South Asian (SAS) AF: 0.287 AC: 1381 AN: 4820

European-Finnish (FIN) AF: 0.165 AC: 1753 AN: 10598

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.194 AC: 13169 AN: 67972

Other (OTH) AF: 0.225 AC: 474 AN: 2106

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
PhyloP100		-1.4
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: rs2073072; hg19: chr20-47269602;