rs10494570

chr1-183847549-G-T

Variant summary

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

The NM_001297671.3(RGL1):c.139-17G>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0826 in 1,601,538 control chromosomes in the GnomAD database, including 5,802 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 0.090 (654 hom., cov: 32)
  • Exomes 𝑓: 0.082 (5148 hom.)
• Consequence: RGL1 NM_001297671.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89

Genes affected

RGL1 (HGNC:30281): (ral guanine nucleotide dissociation stimulator like 1) Predicted to be involved in regulation of catalytic activity. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -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 = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGL1	NM_001297671.3	c.139-17G>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000360851.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGL1	ENST00000360851.4	c.139-17G>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001297671.3	P1
RGL1	ENST00000304685.8	c.244-17G>T		splice_polypyrimidine_tract_variant, intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0901 AC: 13704 AN: 152038 Hom.: 656 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.0802

Gnomad EAS AF: 0.0527

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.0869

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0802

Gnomad OTH AF: 0.0889

GnomAD3 exomes AF: 0.0866 AC: 21287 AN: 245772 Hom.: 986 AF XY: 0.0865 AC XY: 11489 AN XY: 132776

Gnomad AFR exome AF: 0.106

Gnomad AMR exome AF: 0.0984

Gnomad ASJ exome AF: 0.0816

Gnomad EAS exome AF: 0.0441

Gnomad SAS exome AF: 0.112

Gnomad FIN exome AF: 0.0856

Gnomad NFE exome AF: 0.0814

Gnomad OTH exome AF: 0.0861

GnomAD4 exome AF: 0.0819 AC: 118641 AN: 1449382 Hom.: 5148 Cov.: 29 AF XY: 0.0827 AC XY: 59605 AN XY: 720578

Gnomad4 AFR exome AF: 0.108

Gnomad4 AMR exome AF: 0.103

Gnomad4 ASJ exome AF: 0.0840

Gnomad4 EAS exome AF: 0.0510

Gnomad4 SAS exome AF: 0.113

Gnomad4 FIN exome AF: 0.0847

Gnomad4 NFE exome AF: 0.0787

Gnomad4 OTH exome AF: 0.0811

GnomAD4 genome AF: 0.0901 AC: 13710 AN: 152156 Hom.: 654 Cov.: 32 AF XY: 0.0905 AC XY: 6734 AN XY: 74402

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.0802

Gnomad4 EAS AF: 0.0522

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.0869

Gnomad4 NFE AF: 0.0802

Gnomad4 OTH AF: 0.0894

Alfa AF: 0.0824 Hom.: 292

Bravo AF: 0.0918

Asia WGS AF: 0.0730 AC: 255 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	0.66
Dann	Benign	0.47

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: rs10494570; hg19: chr1-183816683;