NM_006909.3:c.634-706A>G

Variant names:

• chr5-81072493-A-G
• rs153227
• NM_006909.3:c.634-706A>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.634-706A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 152,212 control chromosomes in the GnomAD database, including 3,292 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 0.20 (3292 hom., cov: 33)
• Consequence: RASGRF2 NM_006909.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.02
• Publications: 5 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.274 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.634-706A>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.634-706A>G		intron	N/A	ENSP00000265080.4	O14827
	RASGRF2	ENST00000503795.1	TSL:1	n.634-706A>G		intron	N/A	ENSP00000421771.1	D6RAS9
	RASGRF2	ENST00000933988.1		c.634-706A>G		intron	N/A	ENSP00000604047.1

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29961 AN: 152094 Hom.: 3295 Cov.: 33

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.197 AC: 29961 AN: 152212 Hom.: 3292 Cov.: 33 AF XY: 0.197 AC XY: 14632 AN XY: 74430

African (AFR) AF: 0.112 AC: 4637 AN: 41560

American (AMR) AF: 0.281 AC: 4298 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 618 AN: 3470

East Asian (EAS) AF: 0.114 AC: 594 AN: 5196

South Asian (SAS) AF: 0.142 AC: 687 AN: 4822

European-Finnish (FIN) AF: 0.263 AC: 2777 AN: 10568

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.231 AC: 15720 AN: 67984

Other (OTH) AF: 0.180 AC: 380 AN: 2112

Alfa AF: 0.218 Hom.: 5255

Bravo AF: 0.198

Asia WGS AF: 0.133 AC: 464 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.0060
DANN	Benign	0.41
PhyloP100		-4.0
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: rs153227; hg19: chr5-80368312;