rs4809718

Positions:

• chr20-48694450-T-A

Variant summary

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

The NM_020820.4(PREX1):​c.918-1660A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 152,114 control chromosomes in the GnomAD database, including 10,819 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 0.32 (10819 hom., cov: 32)
• Consequence: PREX1 NM_020820.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.973

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PREX1	NM_020820.4	c.918-1660A>T		intron_variant		ENST00000371941.4	NP_065871.3
PREX1	XM_047440331.1	c.393-1660A>T		intron_variant			XP_047296287.1
PREX1	XM_047440332.1	c.393-1660A>T		intron_variant			XP_047296288.1
PREX1	XM_047440333.1	c.393-1660A>T		intron_variant			XP_047296289.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PREX1	ENST00000371941.4	c.918-1660A>T		intron_variant		1	NM_020820.4	ENSP00000361009.3

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48373 AN: 151996 Hom.: 10793 Cov.: 32

Gnomad AFR AF: 0.639

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.0943

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.287

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

GnomAD4 genome AF: 0.318 AC: 48440 AN: 152114 Hom.: 10819 Cov.: 32 AF XY: 0.313 AC XY: 23245 AN XY: 74362

Gnomad4 AFR AF: 0.639

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.232

Gnomad4 EAS AF: 0.0945

Gnomad4 SAS AF: 0.256

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.288

Alfa AF: 0.267 Hom.: 874

Bravo AF: 0.334

Asia WGS AF: 0.219 AC: 763 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.58
DANN	Benign	0.46

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: rs4809718; hg19: chr20-47310988;