Genetic Variant RASGRF1:p.Asn1084Asn (chr15-78985169-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001145648.3(RASGRF1):c.3252T>C(p.Asn1084Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 1,611,868 control chromosomes in the GnomAD database, including 62,195 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 0.30 ( 7355 hom., cov: 32)

Exomes 𝑓: 0.27 ( 54840 hom. )

Consequence

RASGRF1
NM_001145648.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.32

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 made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP7

Synonymous conserved (PhyloP=-2.32 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASGRF1	NM_001145648.3 link	c.3252T>C	p.Asn1084Asn	synonymous_variant	Exon 23 of 27	ENST00000558480.7	NP_001139120.1	Q8IUU5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASGRF1	ENST00000558480.7 link	c.3252T>C	p.Asn1084Asn	synonymous_variant	Exon 23 of 27	2	NM_001145648.3	ENSP00000452781.2		Q13972-3

Frequencies

GnomAD3 genomes

AF:

0.302

AC:

45907

AN:

152000

Hom.:

7347

Cov.:

show subpopulations

Gnomad AFR

AF:

0.410

Gnomad AMI

AF:

0.292

Gnomad AMR

AF:

0.226

Gnomad ASJ

AF:

0.235

Gnomad EAS

AF:

0.191

Gnomad SAS

AF:

0.241

Gnomad FIN

AF:

0.275

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.274

Gnomad OTH

AF:

0.293

GnomAD3 exomes

AF:

0.262

AC:

65769

AN:

251182

Hom.:

9031

AF XY:

0.261

AC XY:

35396

AN XY:

135732

show subpopulations

Gnomad AFR exome

AF:

0.418

Gnomad AMR exome

AF:

0.207

Gnomad ASJ exome

AF:

0.238

Gnomad EAS exome

AF:

0.179

Gnomad SAS exome

AF:

0.236

Gnomad FIN exome

AF:

0.275

Gnomad NFE exome

AF:

0.276

Gnomad OTH exome

AF:

0.269

GnomAD4 exome

AF:

0.271

AC:

395562

AN:

1459750

Hom.:

54840

Cov.:

AF XY:

0.270

AC XY:

196196

AN XY:

726262

show subpopulations

Gnomad4 AFR exome

AF:

0.414

Gnomad4 AMR exome

AF:

0.208

Gnomad4 ASJ exome

AF:

0.239

Gnomad4 EAS exome

AF:

0.209

Gnomad4 SAS exome

AF:

0.236

Gnomad4 FIN exome

AF:

0.274

Gnomad4 NFE exome

AF:

0.275

Gnomad4 OTH exome

AF:

0.272

GnomAD4 genome

AF:

0.302

AC:

45942

AN:

152118

Hom.:

7355

Cov.:

AF XY:

0.298

AC XY:

22139

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.410

Gnomad4 AMR

AF:

0.226

Gnomad4 ASJ

AF:

0.235

Gnomad4 EAS

AF:

0.190

Gnomad4 SAS

AF:

0.241

Gnomad4 FIN

AF:

0.275

Gnomad4 NFE

AF:

0.274

Gnomad4 OTH

AF:

0.291

Alfa

AF:

0.275

Hom.:

8457

Bravo

AF:

0.306

Asia WGS

AF:

0.227

AC:

788

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.029

DANN

Benign

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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