rs4778879

chr15-79080533-A-Gchr15-79080533-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001145648.3(RASGRF1):c.276+9690T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 152,082 control chromosomes in the GnomAD database, including 13,602 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 0.42 (13602 hom., cov: 33)
• Consequence: RASGRF1 NM_001145648.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.378

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RASGRF1	NM_001145648.3	c.276+9690T>C		intron_variant		ENST00000558480.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RASGRF1	ENST00000558480.7	c.276+9690T>C		intron_variant		2	NM_001145648.3	P1
RASGRF1	ENST00000419573.7	c.276+9690T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63813 AN: 151964 Hom.: 13582 Cov.: 33

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.504

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.402

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.420 AC: 63873 AN: 152082 Hom.: 13602 Cov.: 33 AF XY: 0.419 AC XY: 31156 AN XY: 74362

Gnomad4 AFR AF: 0.424

Gnomad4 AMR AF: 0.455

Gnomad4 ASJ AF: 0.378

Gnomad4 EAS AF: 0.506

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.398

Gnomad4 NFE AF: 0.424

Gnomad4 OTH AF: 0.398

Alfa AF: 0.421 Hom.: 2528

Bravo AF: 0.434

Asia WGS AF: 0.304 AC: 1058 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.7
Dann	Benign	0.74

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

LitVar

Other links and lift over

dbSNP: rs4778879; hg19: chr15-79372875;