chr15-78977393-C-G

Position:

• chr15-78977393-C-G

Variant summary

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

The NM_001145648.3(RASGRF1):​c.3494+3227G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 151,686 control chromosomes in the GnomAD database, including 19,448 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 0.46 (19448 hom., cov: 31)
• Consequence: RASGRF1 NM_001145648.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.62

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RASGRF1	NM_001145648.3	c.3494+3227G>C		intron_variant		ENST00000558480.7	NP_001139120.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RASGRF1	ENST00000558480.7	c.3494+3227G>C		intron_variant		2	NM_001145648.3	ENSP00000452781	P1
RASGRF1	ENST00000394745.3	c.1190+3227G>C		intron_variant		1		ENSP00000378228
RASGRF1	ENST00000419573.7	c.3542+3227G>C		intron_variant		2		ENSP00000405963
RASGRF1	ENST00000559926.1	n.198+1535G>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70208 AN: 151570 Hom.: 19444 Cov.: 31

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.624

Gnomad EAS AF: 0.719

Gnomad SAS AF: 0.659

Gnomad FIN AF: 0.584

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.495

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

GnomAD4 genome AF: 0.463 AC: 70218 AN: 151686 Hom.: 19448 Cov.: 31 AF XY: 0.471 AC XY: 34947 AN XY: 74128

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.554

Gnomad4 ASJ AF: 0.624

Gnomad4 EAS AF: 0.719

Gnomad4 SAS AF: 0.660

Gnomad4 FIN AF: 0.584

Gnomad4 NFE AF: 0.577

Gnomad4 OTH AF: 0.498

Alfa AF: 0.379 Hom.: 1164

Bravo AF: 0.442

Asia WGS AF: 0.645 AC: 2243 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	0.037
DANN	Benign	0.45

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: rs1867315; hg19: chr15-79269735;