rs153227

chr5-81072493-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RASGRF2	NM_006909.3	c.634-706A>G		intron_variant		ENST00000265080.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RASGRF2	ENST00000265080.9	c.634-706A>G		intron_variant		1	NM_006909.3	P1

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

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.178

Gnomad4 EAS AF: 0.114

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.263

Gnomad4 NFE AF: 0.231

Gnomad4 OTH AF: 0.180

Alfa AF: 0.219 Hom.: 4566

Bravo AF: 0.198

Asia WGS AF: 0.133 AC: 464 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.0060
Dann	Benign	0.41

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: rs153227; hg19: chr5-80368312;