5-81071815-A-G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASGRF2	NM_006909.3	c.633+1234A>G		intron_variant	Intron 4 of 26	ENST00000265080.9	NP_008840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASGRF2	ENST00000265080.9	c.633+1234A>G		intron_variant	Intron 4 of 26	1	NM_006909.3	ENSP00000265080.4

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

Gnomad4 AFR AF: 0.775

Gnomad4 AMR AF: 0.669

Gnomad4 ASJ AF: 0.597

Gnomad4 EAS AF: 0.723

Gnomad4 SAS AF: 0.696

Gnomad4 FIN AF: 0.763

Gnomad4 NFE AF: 0.682

Gnomad4 OTH AF: 0.677

Alfa AF: 0.676 Hom.: 20983

Bravo AF: 0.707

Asia WGS AF: 0.646 AC: 2229 AN: 3444

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.33

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: rs252587; hg19: chr5-80367634;