1-183847549-G-T

Variant names:

• chr1-183847549-G-T
• rs10494570
• NM_001297671.3:c.139-17G>T

Variant summary

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

The NM_001297671.3(RGL1):​c.139-17G>T variant causes a 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 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89
• Publications: 6 publications found

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

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 = 0.105 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001297671.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGL1	NM_001297671.3	MANE Select	c.139-17G>T		intron	N/A	NP_001284600.1
	RGL1	NM_015149.6		c.244-17G>T		intron	N/A	NP_055964.3
	RGL1	NM_001297669.3		c.133-17G>T		intron	N/A	NP_001284598.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGL1	ENST00000360851.4	TSL:1 MANE Select	c.139-17G>T		intron	N/A	ENSP00000354097.3
	RGL1	ENST00000304685.8	TSL:1	c.244-17G>T		intron	N/A	ENSP00000303192.3

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

GnomAD2 exomes AF: 0.0866 AC: 21287 AN: 245772 AF XY: 0.0865

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 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

African (AFR) AF: 0.108 AC: 3544 AN: 32912

American (AMR) AF: 0.103 AC: 4470 AN: 43450

Ashkenazi Jewish (ASJ) AF: 0.0840 AC: 2165 AN: 25762

East Asian (EAS) AF: 0.0510 AC: 2015 AN: 39544

South Asian (SAS) AF: 0.113 AC: 9550 AN: 84422

European-Finnish (FIN) AF: 0.0847 AC: 4515 AN: 53314

Middle Eastern (MID) AF: 0.116 AC: 657 AN: 5668

European-Non Finnish (NFE) AF: 0.0787 AC: 86872 AN: 1104472

Other (OTH) AF: 0.0811 AC: 4853 AN: 59838

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

African (AFR) AF: 0.107 AC: 4457 AN: 41504

American (AMR) AF: 0.101 AC: 1542 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0802 AC: 278 AN: 3466

East Asian (EAS) AF: 0.0522 AC: 271 AN: 5188

South Asian (SAS) AF: 0.110 AC: 529 AN: 4814

European-Finnish (FIN) AF: 0.0869 AC: 920 AN: 10586

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0802 AC: 5456 AN: 68000

Other (OTH) AF: 0.0894 AC: 188 AN: 2104

Alfa AF: 0.0825 Hom.: 330

Bravo AF: 0.0918

Asia WGS AF: 0.0730 AC: 255 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.66
DANN	Benign	0.47
PhyloP100		-1.9
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: rs10494570; hg19: chr1-183816683;