rs4703822

Positions:

• chr5-81115402-G-A
• chr5-81115402-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006909.3(RASGRF2):​c.2470+1482G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 152,072 control chromosomes in the GnomAD database, including 5,794 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 0.27 (5794 hom., cov: 32)
• Consequence: RASGRF2 NM_006909.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.203

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RASGRF2	NM_006909.3	c.2470+1482G>A		intron_variant		ENST00000265080.9	NP_008840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RASGRF2	ENST00000265080.9	c.2470+1482G>A		intron_variant		1	NM_006909.3	ENSP00000265080	P1
RASGRF2	ENST00000503795.1	c.2470+1482G>A		intron_variant, NMD_transcript_variant		1		ENSP00000421771

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40483 AN: 151952 Hom.: 5797 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.309

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

GnomAD4 genome AF: 0.266 AC: 40485 AN: 152072 Hom.: 5794 Cov.: 32 AF XY: 0.265 AC XY: 19711 AN XY: 74336

Gnomad4 AFR AF: 0.174

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.428

Gnomad4 EAS AF: 0.281

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.312

Gnomad4 OTH AF: 0.306

Alfa AF: 0.311 Hom.: 16651

Bravo AF: 0.264

Asia WGS AF: 0.270 AC: 939 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.20
DANN	Benign	0.48

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: rs4703822; hg19: chr5-80411221;