rs1020720

Variant names:

• chr5-81176949-T-A
• rs1020720
• NM_006909.3:c.2687-3226T>A

Variant summary

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

The NM_006909.3(RASGRF2):​c.2687-3226T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 151,854 control chromosomes in the GnomAD database, including 21,205 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 0.51 (21205 hom., cov: 31)
• Consequence: RASGRF2 NM_006909.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0100
• Publications: 7 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.797 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.2687-3226T>A		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.2687-3226T>A		intron	N/A	ENSP00000265080.4	O14827
	RASGRF2	ENST00000503795.1	TSL:1	n.2687-3226T>A		intron	N/A	ENSP00000421771.1	D6RAS9
	RASGRF2	ENST00000933988.1		c.2642-3226T>A		intron	N/A	ENSP00000604047.1

Frequencies

GnomAD3 genomes AF: 0.507 AC: 76986 AN: 151736 Hom.: 21192 Cov.: 31

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.537

Gnomad EAS AF: 0.816

Gnomad SAS AF: 0.503

Gnomad FIN AF: 0.600

Gnomad MID AF: 0.567

Gnomad NFE AF: 0.604

Gnomad OTH AF: 0.505

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

GnomAD4 genome AF: 0.507 AC: 77028 AN: 151854 Hom.: 21205 Cov.: 31 AF XY: 0.510 AC XY: 37823 AN XY: 74224

African (AFR) AF: 0.281 AC: 11633 AN: 41404

American (AMR) AF: 0.509 AC: 7762 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.537 AC: 1860 AN: 3466

East Asian (EAS) AF: 0.817 AC: 4213 AN: 5154

South Asian (SAS) AF: 0.504 AC: 2412 AN: 4790

European-Finnish (FIN) AF: 0.600 AC: 6328 AN: 10554

Middle Eastern (MID) AF: 0.562 AC: 164 AN: 292

European-Non Finnish (NFE) AF: 0.604 AC: 41032 AN: 67930

Other (OTH) AF: 0.508 AC: 1071 AN: 2110

Alfa AF: 0.542 Hom.: 2987

Bravo AF: 0.488

Asia WGS AF: 0.615 AC: 2136 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.33
DANN	Benign	0.78
PhyloP100		-0.010
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: rs1020720; hg19: chr5-80472768;