rs3743195

Positions:

• chr15-78973524-G-A
• chr15-78973524-G-T

Variant summary

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

The NM_001145648.3(RASGRF1):​c.3495-104C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 805,412 control chromosomes in the GnomAD database, including 39,393 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 0.28 (6371 hom., cov: 32)
  • Exomes 𝑓: 0.31 (33022 hom.)
• Consequence: RASGRF1 NM_001145648.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.420

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RASGRF1	NM_001145648.3	c.3495-104C>T		intron_variant		ENST00000558480.7	NP_001139120.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RASGRF1	ENST00000558480.7	c.3495-104C>T		intron_variant		2	NM_001145648.3	ENSP00000452781.2
RASGRF1	ENST00000394745.3	c.1191-104C>T		intron_variant		1		ENSP00000378228.3
RASGRF1	ENST00000419573.7	c.3543-104C>T		intron_variant		2		ENSP00000405963.3
RASGRF1	ENST00000559926.1	n.199-104C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42008 AN: 151888 Hom.: 6371 Cov.: 32

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.276

GnomAD4 exome AF: 0.312 AC: 203539 AN: 653406 Hom.: 33022 AF XY: 0.309 AC XY: 105816 AN XY: 342328

Gnomad4 AFR exome AF: 0.166

Gnomad4 AMR exome AF: 0.317

Gnomad4 ASJ exome AF: 0.282

Gnomad4 EAS exome AF: 0.170

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.341

Gnomad4 NFE exome AF: 0.335

Gnomad4 OTH exome AF: 0.307

GnomAD4 genome AF: 0.276 AC: 42011 AN: 152006 Hom.: 6371 Cov.: 32 AF XY: 0.273 AC XY: 20286 AN XY: 74292

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.279

Gnomad4 EAS AF: 0.157

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.275

Alfa AF: 0.322 Hom.: 7275

Bravo AF: 0.271

Asia WGS AF: 0.193 AC: 673 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.6
DANN	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs3743195; hg19: chr15-79265866;