Variant rs3816282 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001145648.3(RASGRF1):c.384-17T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,611,864 control chromosomes in the GnomAD database, including 11,086 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 0.095 ( 815 hom., cov: 33)

Exomes 𝑓: 0.11 ( 10271 hom. )

Consequence

RASGRF1
NM_001145648.3 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.392

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RASGRF1	NM_001145648.3 linkuse as main transcript	c.384-17T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000558480.7	NP_001139120.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
RASGRF1	ENST00000558480.7 linkuse as main transcript	c.384-17T>C	splice_polypyrimidine_tract_variant, intron_variant	2	NM_001145648.3	ENSP00000452781	P1	Q13972-3
RASGRF1	ENST00000560334.5 linkuse as main transcript	n.245-17T>C	splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	1
RASGRF1	ENST00000419573.7 linkuse as main transcript	c.384-17T>C	splice_polypyrimidine_tract_variant, intron_variant	2		ENSP00000405963		Q13972-1

Frequencies

GnomAD3 genomes

AF:

0.0951

AC:

14476

AN:

152152

Hom.:

814

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0628

Gnomad AMI

AF:

0.0747

Gnomad AMR

AF:

0.0664

Gnomad ASJ

AF:

0.208

Gnomad EAS

AF:

0.209

Gnomad SAS

AF:

0.244

Gnomad FIN

AF:

0.0877

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.0976

Gnomad OTH

AF:

0.0968

GnomAD3 exomes

AF:

0.119

AC:

29896

AN:

250618

Hom.:

2328

AF XY:

0.128

AC XY:

17285

AN XY:

135432

show subpopulations

Gnomad AFR exome

AF:

0.0625

Gnomad AMR exome

AF:

0.0454

Gnomad ASJ exome

AF:

0.207

Gnomad EAS exome

AF:

0.206

Gnomad SAS exome

AF:

0.244

Gnomad FIN exome

AF:

0.0862

Gnomad NFE exome

AF:

0.100

Gnomad OTH exome

AF:

0.126

GnomAD4 exome

AF:

0.109

AC:

159028

AN:

1459594

Hom.:

10271

Cov.:

AF XY:

0.113

AC XY:

82034

AN XY:

725624

show subpopulations

Gnomad4 AFR exome

AF:

0.0627

Gnomad4 AMR exome

AF:

0.0470

Gnomad4 ASJ exome

AF:

0.208

Gnomad4 EAS exome

AF:

0.193

Gnomad4 SAS exome

AF:

0.241

Gnomad4 FIN exome

AF:

0.0888

Gnomad4 NFE exome

AF:

0.0973

Gnomad4 OTH exome

AF:

0.124

GnomAD4 genome

AF:

0.0951

AC:

14480

AN:

152270

Hom.:

815

Cov.:

AF XY:

0.0966

AC XY:

7191

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0628

Gnomad4 AMR

AF:

0.0663

Gnomad4 ASJ

AF:

0.208

Gnomad4 EAS

AF:

0.208

Gnomad4 SAS

AF:

0.244

Gnomad4 FIN

AF:

0.0877

Gnomad4 NFE

AF:

0.0976

Gnomad4 OTH

AF:

0.0977

Alfa

AF:

0.0954

Hom.:

347

Bravo

AF:

0.0895

Asia WGS

AF:

0.218

AC:

756

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.6

DANN

Benign

0.69

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over