rs6066835

Positions:

• chr20-48738472-T-C

Variant summary

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

The NM_020820.4(PREX1):​c.415-3822A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0928 in 152,256 control chromosomes in the GnomAD database, including 735 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 0.093 (735 hom., cov: 32)
• Consequence: PREX1 NM_020820.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.180

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 (SAS) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PREX1	NM_020820.4	c.415-3822A>G		intron_variant		ENST00000371941.4	NP_065871.3
PREX1	XM_047440331.1	c.-111-3822A>G		intron_variant			XP_047296287.1
PREX1	XM_047440332.1	c.-111-3822A>G		intron_variant			XP_047296288.1
PREX1	XM_047440333.1	c.-111-3822A>G		intron_variant			XP_047296289.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PREX1	ENST00000371941.4	c.415-3822A>G		intron_variant		1	NM_020820.4	ENSP00000361009.3

Frequencies

GnomAD3 genomes AF: 0.0928 AC: 14116 AN: 152138 Hom.: 732 Cov.: 32

Gnomad AFR AF: 0.0925

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.0311

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0840

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.0928 AC: 14132 AN: 152256 Hom.: 735 Cov.: 32 AF XY: 0.0926 AC XY: 6894 AN XY: 74452

Gnomad4 AFR AF: 0.0925

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.166

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.0311

Gnomad4 NFE AF: 0.0840

Gnomad4 OTH AF: 0.118

Alfa AF: 0.0889 Hom.: 548

Bravo AF: 0.0970

Asia WGS AF: 0.158 AC: 550 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	4.4
DANN	Benign	0.33

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: rs6066835; hg19: chr20-47355009;