rs28412916

Positions:

• chr15-79085825-A-C
• chr15-79085825-A-G

Variant summary

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

The NM_001145648.3(RASGRF1):​c.276+4398T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 152,014 control chromosomes in the GnomAD database, including 23,278 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 0.52 (23278 hom., cov: 32)
• Consequence: RASGRF1 NM_001145648.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.198

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RASGRF1	NM_001145648.3	c.276+4398T>G		intron_variant		ENST00000558480.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RASGRF1	ENST00000558480.7	c.276+4398T>G		intron_variant		2	NM_001145648.3	P1
RASGRF1	ENST00000419573.7	c.276+4398T>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79413 AN: 151896 Hom.: 23236 Cov.: 32

Gnomad AFR AF: 0.801

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.506

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.473

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

GnomAD4 genome AF: 0.523 AC: 79517 AN: 152014 Hom.: 23278 Cov.: 32 AF XY: 0.518 AC XY: 38448 AN XY: 74280

Gnomad4 AFR AF: 0.801

Gnomad4 AMR AF: 0.490

Gnomad4 ASJ AF: 0.358

Gnomad4 EAS AF: 0.507

Gnomad4 SAS AF: 0.247

Gnomad4 FIN AF: 0.403

Gnomad4 NFE AF: 0.414

Gnomad4 OTH AF: 0.469

Alfa AF: 0.481 Hom.: 2374

Bravo AF: 0.552

Asia WGS AF: 0.340 AC: 1184 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.0
DANN	Benign	0.58

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: rs28412916; hg19: chr15-79378167;