rs13044736

Positions:

• chr20-48803368-A-G

Variant summary

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

The NM_020820.4(PREX1):​c.219+24274T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 151,906 control chromosomes in the GnomAD database, including 11,277 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 0.38 (11277 hom., cov: 31)
• Consequence: PREX1 NM_020820.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.386

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PREX1	NM_020820.4	c.219+24274T>C		intron_variant		ENST00000371941.4
PREX1	XM_047440331.1	c.-307+16132T>C		intron_variant
PREX1	XM_047440332.1	c.-307+18038T>C		intron_variant
PREX1	XM_047440333.1	c.-307+46067T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PREX1	ENST00000371941.4	c.219+24274T>C		intron_variant		1	NM_020820.4	P1

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57405 AN: 151788 Hom.: 11254 Cov.: 31

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.374

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

GnomAD4 genome AF: 0.378 AC: 57467 AN: 151906 Hom.: 11277 Cov.: 31 AF XY: 0.377 AC XY: 28003 AN XY: 74248

Gnomad4 AFR AF: 0.333

Gnomad4 AMR AF: 0.397

Gnomad4 ASJ AF: 0.366

Gnomad4 EAS AF: 0.133

Gnomad4 SAS AF: 0.326

Gnomad4 FIN AF: 0.391

Gnomad4 NFE AF: 0.422

Gnomad4 OTH AF: 0.379

Alfa AF: 0.413 Hom.: 1615

Bravo AF: 0.376

Asia WGS AF: 0.298 AC: 1040 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.31

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: rs13044736; hg19: chr20-47419905;