chr20-48624820-C-T

Position:

• chr20-48624820-C-T

Variant summary

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

The NM_020820.4(PREX1):​c.*1065G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 152,294 control chromosomes in the GnomAD database, including 2,844 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 (2843 hom., cov: 33)
  • Exomes 𝑓: 0.13 (1 hom.)
• Consequence: PREX1 NM_020820.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.107

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 = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PREX1	NM_020820.4	c.*1065G>A		3_prime_UTR_variant	40/40	ENST00000371941.4	NP_065871.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PREX1	ENST00000371941.4	c.*1065G>A		3_prime_UTR_variant	40/40	1	NM_020820.4	ENSP00000361009	P1
PREX1	ENST00000482556.5	c.*1463G>A		3_prime_UTR_variant, NMD_transcript_variant	22/22	2		ENSP00000434632

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29175 AN: 152106 Hom.: 2841 Cov.: 33

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.283

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.220

GnomAD4 exome AF: 0.129 AC: 9 AN: 70 Hom.: 1 Cov.: 0 AF XY: 0.0926 AC XY: 5 AN XY: 54

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.143

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.192 AC: 29201 AN: 152224 Hom.: 2843 Cov.: 33 AF XY: 0.191 AC XY: 14209 AN XY: 74410

Gnomad4 AFR AF: 0.174

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.122

Gnomad4 SAS AF: 0.266

Gnomad4 FIN AF: 0.169

Gnomad4 NFE AF: 0.194

Gnomad4 OTH AF: 0.222

Alfa AF: 0.197 Hom.: 2994

Bravo AF: 0.192

Asia WGS AF: 0.197 AC: 687 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	2.2
DANN	Benign	0.67

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: rs2664570; hg19: chr20-47241358;