NM_006909.3:c.633+1234A>G

Variant names:

• chr5-81071815-A-G
• rs252587
• NM_006909.3:c.633+1234A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006909.3(RASGRF2):​c.633+1234A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.711 in 151,880 control chromosomes in the GnomAD database, including 38,661 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 0.71 (38661 hom., cov: 31)
• Consequence: RASGRF2 NM_006909.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0530
• Publications: 3 publications found

Genes affected

RASGRF2 (HGNC:9876): (Ras protein specific guanine nucleotide releasing factor 2) RAS GTPases cycle between an inactive GDP-bound state and an active GTP-bound state. This gene encodes a calcium-regulated nucleotide exchange factor activating both RAS and RAS-related protein, RAC1, through the exchange of bound GDP for GTP, thereby, coordinating the signaling of distinct mitogen-activated protein kinase pathways. [provided by RefSeq, Oct 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006909.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASGRF2	NM_006909.3	MANE Select	c.633+1234A>G		intron	N/A	NP_008840.1	O14827

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASGRF2	ENST00000265080.9	TSL:1 MANE Select	c.633+1234A>G		intron	N/A	ENSP00000265080.4	O14827
	RASGRF2	ENST00000503795.1	TSL:1	n.633+1234A>G		intron	N/A	ENSP00000421771.1	D6RAS9
	RASGRF2	ENST00000933988.1		c.633+1234A>G		intron	N/A	ENSP00000604047.1

Frequencies

GnomAD3 genomes AF: 0.711 AC: 107957 AN: 151762 Hom.: 38622 Cov.: 31

Gnomad AFR AF: 0.775

Gnomad AMI AF: 0.712

Gnomad AMR AF: 0.670

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.722

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.763

Gnomad MID AF: 0.561

Gnomad NFE AF: 0.682

Gnomad OTH AF: 0.682

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

GnomAD4 genome AF: 0.711 AC: 108041 AN: 151880 Hom.: 38661 Cov.: 31 AF XY: 0.713 AC XY: 52943 AN XY: 74228

African (AFR) AF: 0.775 AC: 32093 AN: 41420

American (AMR) AF: 0.669 AC: 10221 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.597 AC: 2071 AN: 3468

East Asian (EAS) AF: 0.723 AC: 3738 AN: 5170

South Asian (SAS) AF: 0.696 AC: 3357 AN: 4822

European-Finnish (FIN) AF: 0.763 AC: 8007 AN: 10500

Middle Eastern (MID) AF: 0.558 AC: 163 AN: 292

European-Non Finnish (NFE) AF: 0.682 AC: 46316 AN: 67918

Other (OTH) AF: 0.677 AC: 1426 AN: 2106

Alfa AF: 0.692 Hom.: 39839

Bravo AF: 0.707

Asia WGS AF: 0.646 AC: 2229 AN: 3444

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.33
PhyloP100		-0.053
Mutation Taster		=100/0	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: rs252587; hg19: chr5-80367634;