rs2426087

Positions:

• chr20-48763274-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_020820.4(PREX1):​c.220-15394C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0197 in 152,358 control chromosomes in the GnomAD database, including 36 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 0.020 (36 hom., cov: 32)
• Consequence: PREX1 NM_020820.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.402

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=-0.75).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0197 (3003/152358) while in subpopulation NFE AF= 0.0291 (1977/68024). AF 95% confidence interval is 0.028. There are 36 homozygotes in gnomad4. There are 1349 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 3003 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PREX1	NM_020820.4	c.220-15394C>T		intron_variant		ENST00000371941.4	NP_065871.3
PREX1	XM_047440331.1	c.-306-15394C>T		intron_variant			XP_047296287.1
PREX1	XM_047440332.1	c.-306-15394C>T		intron_variant			XP_047296288.1
PREX1	XM_047440333.1	c.-306-15394C>T		intron_variant			XP_047296289.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PREX1	ENST00000371941.4	c.220-15394C>T		intron_variant		1	NM_020820.4	ENSP00000361009.3

Frequencies

GnomAD3 genomes AF: 0.0197 AC: 3005 AN: 152240 Hom.: 37 Cov.: 32

Gnomad AFR AF: 0.00608

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.0258

Gnomad ASJ AF: 0.0395

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0149

Gnomad FIN AF: 0.00480

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0291

Gnomad OTH AF: 0.0315

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

GnomAD4 genome AF: 0.0197 AC: 3003 AN: 152358 Hom.: 36 Cov.: 32 AF XY: 0.0181 AC XY: 1349 AN XY: 74508

Gnomad4 AFR AF: 0.00606

Gnomad4 AMR AF: 0.0259

Gnomad4 ASJ AF: 0.0395

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0151

Gnomad4 FIN AF: 0.00480

Gnomad4 NFE AF: 0.0291

Gnomad4 OTH AF: 0.0307

Alfa AF: 0.0221 Hom.: 8

Bravo AF: 0.0206

Asia WGS AF: 0.00606 AC: 21 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	8.1
DANN	Benign	0.91

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: rs2426087; hg19: chr20-47379811; COSMIC: COSV64249547;