chr20-48636949-T-C

Variant names:

• chr20-48636949-T-C
• rs3935549
• NM_020820.4:c.3947-266A>G

Variant summary

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

The NM_020820.4(PREX1):​c.3947-266A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 152,138 control chromosomes in the GnomAD database, including 31,010 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 0.61 (31010 hom., cov: 33)
• Consequence: PREX1 NM_020820.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.96
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PREX1	NM_020820.4	c.3947-266A>G		intron_variant	Intron 31 of 39	ENST00000371941.4	NP_065871.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PREX1	ENST00000371941.4	c.3947-266A>G		intron_variant	Intron 31 of 39	1	NM_020820.4	ENSP00000361009.3
PREX1	ENST00000482556.5	n.1910-266A>G		intron_variant	Intron 14 of 21	2		ENSP00000434632.1

Frequencies

GnomAD3 genomes AF: 0.608 AC: 92440 AN: 152020 Hom.: 30944 Cov.: 33

Gnomad AFR AF: 0.907

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.574

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.614

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

GnomAD4 genome AF: 0.608 AC: 92565 AN: 152138 Hom.: 31010 Cov.: 33 AF XY: 0.604 AC XY: 44900 AN XY: 74354

African (AFR) AF: 0.908 AC: 37729 AN: 41564

American (AMR) AF: 0.574 AC: 8782 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 1981 AN: 3470

East Asian (EAS) AF: 0.428 AC: 2208 AN: 5154

South Asian (SAS) AF: 0.663 AC: 3199 AN: 4824

European-Finnish (FIN) AF: 0.395 AC: 4173 AN: 10554

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.480 AC: 32600 AN: 67964

Other (OTH) AF: 0.618 AC: 1305 AN: 2112

Alfa AF: 0.543 Hom.: 4167

Bravo AF: 0.629

Asia WGS AF: 0.587 AC: 2043 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.68
PhyloP100		-2.0
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: rs3935549; hg19: chr20-47253487;