dbSNP rs10797919: RGL1:c.611-6G>C (chr1-183883780-G-C) – 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.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

Publications

26 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=-0.76).

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 rank	MANE	Protein	UniProt
RGL1	NM_001297671.3 link	c.611-6G>C		splice_region_variant, intron_variant	Intron 5 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.611-6G>C		splice_region_variant, intron_variant	Intron 5 of 17	1	NM_001297671.3	ENSP00000354097.3
RGL1	ENST00000304685.8 link	c.716-6G>C		splice_region_variant, intron_variant	Intron 6 of 18	1		ENSP00000303192.3

Frequencies

GnomAD3 genomes

AF:

0.441

AC:

67050

AN:

151906

Hom.:

14974

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.424

AC:

106338

AN:

250874

AF XY:

0.420

show subpopulations

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 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.:

AF XY:

0.431

AC XY:

313367

AN XY:

726466

show subpopulations

African (AFR)

AF:

0.456

AC:

15234

AN:

33440

American (AMR)

AF:

0.372

AC:

16621

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.353

AC:

9224

AN:

26116

East Asian (EAS)

AF:

0.515

AC:

20422

AN:

39680

South Asian (SAS)

AF:

0.384

AC:

33124

AN:

86202

European-Finnish (FIN)

AF:

0.461

AC:

24623

AN:

53382

Middle Eastern (MID)

AF:

0.311

AC:

1791

AN:

5756

European-Non Finnish (NFE)

AF:

0.439

AC:

487048

AN:

1110534

Other (OTH)

AF:

0.431

AC:

26000

AN:

60338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

16184

32368

48553

64737

80921

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14848

29696

44544

59392

74240

<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:

0.441

AC:

67069

AN:

152024

Hom.:

14973

Cov.:

AF XY:

0.440

AC XY:

32710

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.466

AC:

19296

AN:

41422

American (AMR)

AF:

0.401

AC:

6139

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.350

AC:

1215

AN:

3472

East Asian (EAS)

AF:

0.506

AC:

2608

AN:

5158

South Asian (SAS)

AF:

0.401

AC:

1931

AN:

4818

European-Finnish (FIN)

AF:

0.468

AC:

4949

AN:

10566

Middle Eastern (MID)

AF:

0.279

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.435

AC:

29555

AN:

67978

Other (OTH)

AF:

0.400

AC:

845

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1953

3905

5858

7810

9763

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

620

1240

1860

2480

3100

<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:

0.428

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

(source)

DANN

Benign

0.61

PhyloP100

1.5

Mutation Taster

=92/8

polymorphism (auto)

(source)

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

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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