5-81016398-C-T

Variant names:

• chr5-81016398-C-T
• rs533308
• NM_006909.3:c.289-26479C>T

Variant summary

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

The NM_006909.3(RASGRF2):​c.289-26479C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.816 in 152,144 control chromosomes in the GnomAD database, including 51,090 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 0.82 (51090 hom., cov: 32)
• Consequence: RASGRF2 NM_006909.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.165
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.838 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASGRF2	NM_006909.3	MANE Select	c.289-26479C>T		intron	N/A	NP_008840.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASGRF2	ENST00000265080.9	TSL:1 MANE Select	c.289-26479C>T		intron	N/A	ENSP00000265080.4
	RASGRF2	ENST00000503795.1	TSL:1	n.289-26479C>T		intron	N/A	ENSP00000421771.1
	RASGRF2	ENST00000933988.1		c.289-26479C>T		intron	N/A	ENSP00000604047.1

Frequencies

GnomAD3 genomes AF: 0.816 AC: 124035 AN: 152026 Hom.: 51041 Cov.: 32

Gnomad AFR AF: 0.846

Gnomad AMI AF: 0.830

Gnomad AMR AF: 0.851

Gnomad ASJ AF: 0.843

Gnomad EAS AF: 0.525

Gnomad SAS AF: 0.838

Gnomad FIN AF: 0.699

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.826

Gnomad OTH AF: 0.838

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

GnomAD4 genome AF: 0.816 AC: 124140 AN: 152144 Hom.: 51090 Cov.: 32 AF XY: 0.809 AC XY: 60200 AN XY: 74374

African (AFR) AF: 0.846 AC: 35104 AN: 41512

American (AMR) AF: 0.851 AC: 12996 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.843 AC: 2926 AN: 3472

East Asian (EAS) AF: 0.525 AC: 2712 AN: 5166

South Asian (SAS) AF: 0.839 AC: 4039 AN: 4816

European-Finnish (FIN) AF: 0.699 AC: 7388 AN: 10568

Middle Eastern (MID) AF: 0.929 AC: 273 AN: 294

European-Non Finnish (NFE) AF: 0.826 AC: 56175 AN: 68014

Other (OTH) AF: 0.839 AC: 1770 AN: 2110

Alfa AF: 0.830 Hom.: 29047

Bravo AF: 0.829

Asia WGS AF: 0.698 AC: 2428 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.3
DANN	Benign	0.41
PhyloP100		-0.17
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: rs533308; hg19: chr5-80312217;