NM_001145648.3:c.3494+3227G>C

Variant names:

• chr15-78977393-C-G
• rs1867315
• NM_001145648.3:c.3494+3227G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RASGRF1	NM_001145648.3	c.3494+3227G>C		intron_variant	Intron 24 of 26	ENST00000558480.7	NP_001139120.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASGRF1	ENST00000558480.7	c.3494+3227G>C		intron_variant	Intron 24 of 26	2	NM_001145648.3	ENSP00000452781.2
RASGRF1	ENST00000394745.3	c.1190+3227G>C		intron_variant	Intron 11 of 13	1		ENSP00000378228.3
RASGRF1	ENST00000419573.7	c.3542+3227G>C		intron_variant	Intron 25 of 27	2		ENSP00000405963.3
RASGRF1	ENST00000559926.1	n.198+1535G>C		intron_variant	Intron 1 of 2	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

African (AFR) AF: 0.136 AC: 5619 AN: 41298

American (AMR) AF: 0.554 AC: 8450 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.624 AC: 2165 AN: 3468

East Asian (EAS) AF: 0.719 AC: 3702 AN: 5148

South Asian (SAS) AF: 0.660 AC: 3174 AN: 4808

European-Finnish (FIN) AF: 0.584 AC: 6133 AN: 10502

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.577 AC: 39204 AN: 67916

Other (OTH) AF: 0.498 AC: 1048 AN: 2104

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
PhyloP100		-3.6
Mutation Taster		=94/6	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1867315; hg19: chr15-79269735;