rs10797919

Positions:

• chr1-183883780-G-C
• chr1-183883780-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.611-6G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 1,612,180 control chromosomes in the GnomAD database, including 153,995 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.44 (14973 hom., cov: 32)
  • Exomes 𝑓: 0.43 (139022 hom.)
• Consequence: RGL1 NM_001297671.3 splice_region, intron
• Scores: Splicing: ADA: 0.00004389
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.48

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=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGL1	NM_001297671.3	c.611-6G>C		splice_region_variant, intron_variant		ENST00000360851.4	NP_001284600.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGL1	ENST00000360851.4	c.611-6G>C		splice_region_variant, intron_variant		1	NM_001297671.3	ENSP00000354097.3
RGL1	ENST00000304685.8	c.716-6G>C		splice_region_variant, intron_variant		1		ENSP00000303192.3

Frequencies

GnomAD3 genomes AF: 0.441 AC: 67050 AN: 151906 Hom.: 14974 Cov.: 32

Gnomad AFR AF: 0.466

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.505

Gnomad SAS AF: 0.402

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.403

GnomAD3 exomes AF: 0.424 AC: 106338 AN: 250874 Hom.: 22861 AF XY: 0.420 AC XY: 56971 AN XY: 135562

Gnomad AFR exome AF: 0.471

Gnomad AMR exome AF: 0.363

Gnomad ASJ exome AF: 0.351

Gnomad EAS exome AF: 0.509

Gnomad SAS exome AF: 0.385

Gnomad FIN exome AF: 0.466

Gnomad NFE exome AF: 0.431

Gnomad OTH exome AF: 0.414

GnomAD4 exome AF: 0.434 AC: 634087 AN: 1460156 Hom.: 139022 Cov.: 37 AF XY: 0.431 AC XY: 313367 AN XY: 726466

Gnomad4 AFR exome AF: 0.456

Gnomad4 AMR exome AF: 0.372

Gnomad4 ASJ exome AF: 0.353

Gnomad4 EAS exome AF: 0.515

Gnomad4 SAS exome AF: 0.384

Gnomad4 FIN exome AF: 0.461

Gnomad4 NFE exome AF: 0.439

Gnomad4 OTH exome AF: 0.431

GnomAD4 genome AF: 0.441 AC: 67069 AN: 152024 Hom.: 14973 Cov.: 32 AF XY: 0.440 AC XY: 32710 AN XY: 74314

Gnomad4 AFR AF: 0.466

Gnomad4 AMR AF: 0.401

Gnomad4 ASJ AF: 0.350

Gnomad4 EAS AF: 0.506

Gnomad4 SAS AF: 0.401

Gnomad4 FIN AF: 0.468

Gnomad4 NFE AF: 0.435

Gnomad4 OTH AF: 0.400

Alfa AF: 0.428 Hom.: 10612

Bravo AF: 0.436

Asia WGS AF: 0.460 AC: 1603 AN: 3478

EpiCase AF: 0.418

EpiControl AF: 0.407

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	9.1
DANN	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000044
dbscSNV1_RF	Benign	0.0020
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: rs10797919; hg19: chr1-183852914; COSMIC: COSV58995747;