Genetic Variant RGL1:c.139-17G>T (chr1-183847549-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.89

Publications

6 publications found

Variant links:

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]

RGL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGL1	NM_001297671.3 link	c.139-17G>T		intron_variant	Intron 2 of 17	ENST00000360851.4	NP_001284600.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGL1	ENST00000360851.4 link	c.139-17G>T		intron_variant	Intron 2 of 17	1	NM_001297671.3	ENSP00000354097.3
RGL1	ENST00000304685.8 link	c.244-17G>T		intron_variant	Intron 3 of 18	1		ENSP00000303192.3

Frequencies

GnomAD3 genomes

AF:

0.0901

AC:

13704

AN:

152038

Hom.:

656

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0827

AC XY:

59605

AN XY:

720578

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

5180

10361

15541

20722

25902

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3250

6500

9750

13000

16250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0901

AC:

13710

AN:

152156

Hom.:

654

Cov.:

AF XY:

0.0905

AC XY:

6734

AN XY:

74402

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.0802

AC:

5456

AN:

68000

Other (OTH)

AF:

0.0894

AC:

188

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

643

1287

1930

2574

3217

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

296

444

592

740

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.66

(source)

DANN

Benign

0.47

PhyloP100

-1.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over