rs888817

Variant names:

• chr5-80961979-G-A
• rs888817
• NM_006909.3:c.288+953G>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.288+953G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.678 in 152,106 control chromosomes in the GnomAD database, including 35,489 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 0.68 (35489 hom., cov: 32)
• Consequence: RASGRF2 NM_006909.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.377
• Publications: 8 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=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASGRF2	NM_006909.3	c.288+953G>A		intron_variant	Intron 1 of 26	ENST00000265080.9	NP_008840.1
RASGRF2	XM_005248565.2	c.288+953G>A		intron_variant	Intron 1 of 18		XP_005248622.1
RASGRF2	XM_017009683.2	c.288+953G>A		intron_variant	Intron 1 of 17		XP_016865172.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASGRF2	ENST00000265080.9	c.288+953G>A		intron_variant	Intron 1 of 26	1	NM_006909.3	ENSP00000265080.4
RASGRF2	ENST00000503795.1	n.288+953G>A		intron_variant	Intron 1 of 27	1		ENSP00000421771.1
RASGRF2	ENST00000638442.1	c.288+953G>A		intron_variant	Intron 1 of 9	5		ENSP00000491428.1

Frequencies

GnomAD3 genomes AF: 0.678 AC: 103015 AN: 151988 Hom.: 35440 Cov.: 32

Gnomad AFR AF: 0.788

Gnomad AMI AF: 0.694

Gnomad AMR AF: 0.633

Gnomad ASJ AF: 0.739

Gnomad EAS AF: 0.504

Gnomad SAS AF: 0.721

Gnomad FIN AF: 0.608

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.638

Gnomad OTH AF: 0.664

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

GnomAD4 genome AF: 0.678 AC: 103117 AN: 152106 Hom.: 35489 Cov.: 32 AF XY: 0.676 AC XY: 50254 AN XY: 74328

African (AFR) AF: 0.789 AC: 32751 AN: 41514

American (AMR) AF: 0.632 AC: 9657 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.739 AC: 2566 AN: 3470

East Asian (EAS) AF: 0.504 AC: 2600 AN: 5162

South Asian (SAS) AF: 0.722 AC: 3481 AN: 4822

European-Finnish (FIN) AF: 0.608 AC: 6425 AN: 10566

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.638 AC: 43399 AN: 67986

Other (OTH) AF: 0.662 AC: 1395 AN: 2106

Alfa AF: 0.653 Hom.: 126472

Bravo AF: 0.684

Asia WGS AF: 0.593 AC: 2060 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	9.0
DANN	Benign	0.81
PhyloP100		-0.38
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: rs888817; hg19: chr5-80257798;