chr20-48691396-A-G

Variant names:

• chr20-48691396-A-G
• rs3746819
• NM_020820.4:c.1037-300T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020820.4(PREX1):​c.1037-300T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0667 in 152,164 control chromosomes in the GnomAD database, including 395 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 0.067 (395 hom., cov: 32)
• Consequence: PREX1 NM_020820.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0480
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PREX1	NM_020820.4	c.1037-300T>C		intron_variant	Intron 8 of 39	ENST00000371941.4	NP_065871.3
PREX1	XM_047440331.1	c.512-300T>C		intron_variant	Intron 9 of 40		XP_047296287.1
PREX1	XM_047440332.1	c.512-300T>C		intron_variant	Intron 8 of 39		XP_047296288.1
PREX1	XM_047440333.1	c.512-300T>C		intron_variant	Intron 9 of 40		XP_047296289.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PREX1	ENST00000371941.4	c.1037-300T>C		intron_variant	Intron 8 of 39	1	NM_020820.4	ENSP00000361009.3

Frequencies

GnomAD3 genomes AF: 0.0667 AC: 10147 AN: 152046 Hom.: 396 Cov.: 32

Gnomad AFR AF: 0.0254

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0842

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.0471

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0765

Gnomad OTH AF: 0.0856

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

GnomAD4 genome AF: 0.0667 AC: 10144 AN: 152164 Hom.: 395 Cov.: 32 AF XY: 0.0674 AC XY: 5014 AN XY: 74404

African (AFR) AF: 0.0253 AC: 1049 AN: 41514

American (AMR) AF: 0.102 AC: 1552 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0842 AC: 292 AN: 3468

East Asian (EAS) AF: 0.127 AC: 657 AN: 5182

South Asian (SAS) AF: 0.127 AC: 612 AN: 4812

European-Finnish (FIN) AF: 0.0471 AC: 499 AN: 10594

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0765 AC: 5200 AN: 67990

Other (OTH) AF: 0.0842 AC: 178 AN: 2114

Alfa AF: 0.0668 Hom.: 52

Bravo AF: 0.0673

Asia WGS AF: 0.106 AC: 367 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.6
DANN	Benign	0.41
PhyloP100		0.048
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3746819; hg19: chr20-47307934;