dbSNP rs3743200: RASGRF1:c.3415-1005G>A (chr15-78981704-C-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_001145648.3(RASGRF1):c.3415-1005G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 152,214 control chromosomes in the GnomAD database, including 4,361 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 0.24 ( 4361 hom., cov: 33)

Exomes 𝑓: 0.21 ( 0 hom. )

Consequence

RASGRF1
NM_001145648.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.194

Publications

19 publications found

Variant links:

Genes affected

RASGRF1 (HGNC:9875): (Ras protein specific guanine nucleotide releasing factor 1) The protein encoded by this gene is a guanine nucleotide exchange factor (GEF) similar to the Saccharomyces cerevisiae CDC25 gene product. Functional analysis has demonstrated that this protein stimulates the dissociation of GDP from RAS protein. The studies of the similar gene in mouse suggested that the Ras-GEF activity of this protein in brain can be activated by Ca2+ influx, muscarinic receptors, and G protein beta-gamma subunit. Mouse studies also indicated that the Ras-GEF signaling pathway mediated by this protein may be important for long-term memory. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Mar 2009]

RASGRF1 links:

ENSG00000177699 (HGNC:):

ENSG00000177699 links:

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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=-0.87).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASGRF1	NM_001145648.3 link	c.3415-1005G>A		intron_variant	Intron 23 of 26	ENST00000558480.7	NP_001139120.1	Q8IUU5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASGRF1	ENST00000558480.7 link	c.3415-1005G>A		intron_variant	Intron 23 of 26	2	NM_001145648.3	ENSP00000452781.2		Q13972-3

Frequencies

GnomAD3 genomes

AF:

0.237

AC:

35999

AN:

152038

Hom.:

4358

Cov.:

show subpopulations

Gnomad AFR

AF:

0.232

Gnomad AMI

AF:

0.209

Gnomad AMR

AF:

0.193

Gnomad ASJ

AF:

0.212

Gnomad EAS

AF:

0.190

Gnomad SAS

AF:

0.227

Gnomad FIN

AF:

0.267

Gnomad MID

AF:

0.239

Gnomad NFE

AF:

0.251

Gnomad OTH

AF:

0.233

GnomAD4 exome

AF:

0.207

AC:

AN:

Hom.:

Cov.:

AF XY:

0.222

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.222

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.237

AC:

36024

AN:

152156

Hom.:

4361

Cov.:

AF XY:

0.235

AC XY:

17444

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.232

AC:

9633

AN:

41506

American (AMR)

AF:

0.192

AC:

2945

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.212

AC:

734

AN:

3470

East Asian (EAS)

AF:

0.189

AC:

980

AN:

5184

South Asian (SAS)

AF:

0.227

AC:

1094

AN:

4816

European-Finnish (FIN)

AF:

0.267

AC:

2822

AN:

10572

Middle Eastern (MID)

AF:

0.240

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.251

AC:

17067

AN:

67994

Other (OTH)

AF:

0.232

AC:

489

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1468

2937

4405

5874

7342

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

394

788

1182

1576

1970

<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:

0.244

Hom.:

15157

Bravo

AF:

0.234

Asia WGS

AF:

0.213

AC:

742

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.86

(source)

DANN

Benign

0.60

PhyloP100

-0.19

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over