chr19-11390564-A-G

Variant names:

• chr19-11390564-A-G
• rs318699
• ENST00000562663.5:n.*1249-5920T>C

Variant summary

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

The ENST00000562663.5(RGL3):​n.*1249-5920T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.727 in 151,520 control chromosomes in the GnomAD database, including 41,107 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 0.73 (41107 hom., cov: 28)
• Consequence: RGL3 ENST00000562663.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.789
• Publications: 12 publications found

Genes affected

RGL3 (HGNC:30282): (ral guanine nucleotide dissociation stimulator like 3) Predicted to enable guanyl-nucleotide exchange factor activity and small GTPase binding activity. Predicted to be involved in positive regulation of GTPase activity and small GTPase mediated signal transduction. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.908 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGL3	ENST00000562663.5	n.*1249-5920T>C		intron_variant	Intron 18 of 18	5		ENSP00000454678.1
RGL3	ENST00000563726.5	n.*1656-5920T>C		intron_variant	Intron 19 of 19	2		ENSP00000455922.1

Frequencies

GnomAD3 genomes AF: 0.727 AC: 110025 AN: 151402 Hom.: 41054 Cov.: 28

Gnomad AFR AF: 0.916

Gnomad AMI AF: 0.484

Gnomad AMR AF: 0.727

Gnomad ASJ AF: 0.636

Gnomad EAS AF: 0.682

Gnomad SAS AF: 0.667

Gnomad FIN AF: 0.650

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.640

Gnomad OTH AF: 0.724

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

GnomAD4 genome AF: 0.727 AC: 110143 AN: 151520 Hom.: 41107 Cov.: 28 AF XY: 0.727 AC XY: 53751 AN XY: 73984

African (AFR) AF: 0.916 AC: 37842 AN: 41326

American (AMR) AF: 0.727 AC: 11013 AN: 15150

Ashkenazi Jewish (ASJ) AF: 0.636 AC: 2205 AN: 3468

East Asian (EAS) AF: 0.682 AC: 3497 AN: 5128

South Asian (SAS) AF: 0.667 AC: 3199 AN: 4796

European-Finnish (FIN) AF: 0.650 AC: 6822 AN: 10490

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.640 AC: 43418 AN: 67868

Other (OTH) AF: 0.723 AC: 1510 AN: 2088

Alfa AF: 0.668 Hom.: 62889

Bravo AF: 0.742

Asia WGS AF: 0.719 AC: 2503 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.92
DANN	Benign	0.68
PhyloP100		-0.79

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs318699; hg19: chr19-11501240;