rs3743200

Positions:

• chr15-78981704-C-T

Variant summary

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

The NM_001145648.3(RASGRF1):​c.3415-1005G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 152,214 control chromosomes in the GnomAD database, including 4,361 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 0.24 (4361 hom., cov: 33)
  • Exomes 𝑓: 0.21 (0 hom.)
• Consequence: RASGRF1 NM_001145648.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.194

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RASGRF1	NM_001145648.3	c.3415-1005G>A		intron_variant		ENST00000558480.7	NP_001139120.1
LOC100129540	NR_148998.1	n.435+2381C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RASGRF1	ENST00000558480.7	c.3415-1005G>A		intron_variant		2	NM_001145648.3	ENSP00000452781	P1
	ENST00000316148.4	n.435+2381C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.237 AC: 35999 AN: 152038 Hom.: 4358 Cov.: 33

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.233

GnomAD4 exome AF: 0.207 AC: 12 AN: 58 Hom.: 0 Cov.: 0 AF XY: 0.222 AC XY: 8 AN XY: 36

Gnomad4 AFR exome AF: 0.00

Gnomad4 NFE exome AF: 0.222

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.237 AC: 36024 AN: 152156 Hom.: 4361 Cov.: 33 AF XY: 0.235 AC XY: 17444 AN XY: 74376

Gnomad4 AFR AF: 0.232

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.212

Gnomad4 EAS AF: 0.189

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.267

Gnomad4 NFE AF: 0.251

Gnomad4 OTH AF: 0.232

Alfa AF: 0.245 Hom.: 7044

Bravo AF: 0.234

Asia WGS AF: 0.213 AC: 742 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.86
DANN	Benign	0.60

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

Other links and lift over

dbSNP: rs3743200; hg19: chr15-79274046;