rs35000

Variant names:

• chr5-80981417-T-C
• rs35000
• NM_006909.3:c.288+20391T>C

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+20391T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.67 in 152,002 control chromosomes in the GnomAD database, including 34,241 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 0.67 (34241 hom., cov: 31)
• Consequence: RASGRF2 NM_006909.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.970
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASGRF2	NM_006909.3	c.288+20391T>C		intron_variant	Intron 1 of 26	ENST00000265080.9	NP_008840.1
RASGRF2	XM_047417464.1	c.-85+4616T>C		intron_variant	Intron 1 of 26		XP_047273420.1
RASGRF2	XM_005248565.2	c.288+20391T>C		intron_variant	Intron 1 of 18		XP_005248622.1
RASGRF2	XM_017009683.2	c.288+20391T>C		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+20391T>C		intron_variant	Intron 1 of 26	1	NM_006909.3	ENSP00000265080.4
RASGRF2	ENST00000503795.1	n.288+20391T>C		intron_variant	Intron 1 of 27	1		ENSP00000421771.1
RASGRF2	ENST00000638442.1	c.288+20391T>C		intron_variant	Intron 1 of 9	5		ENSP00000491428.1

Frequencies

GnomAD3 genomes AF: 0.670 AC: 101758 AN: 151884 Hom.: 34215 Cov.: 31

Gnomad AFR AF: 0.682

Gnomad AMI AF: 0.636

Gnomad AMR AF: 0.685

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.764

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.613

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.664

Gnomad OTH AF: 0.663

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

GnomAD4 genome AF: 0.670 AC: 101834 AN: 152002 Hom.: 34241 Cov.: 31 AF XY: 0.667 AC XY: 49560 AN XY: 74276

African (AFR) AF: 0.682 AC: 28277 AN: 41448

American (AMR) AF: 0.684 AC: 10456 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.642 AC: 2227 AN: 3470

East Asian (EAS) AF: 0.765 AC: 3950 AN: 5162

South Asian (SAS) AF: 0.650 AC: 3120 AN: 4800

European-Finnish (FIN) AF: 0.613 AC: 6477 AN: 10560

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.664 AC: 45144 AN: 67966

Other (OTH) AF: 0.662 AC: 1398 AN: 2112

Alfa AF: 0.668 Hom.: 17934

Bravo AF: 0.679

Asia WGS AF: 0.718 AC: 2494 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.24
DANN	Benign	0.59
PhyloP100		-0.97
Mutation Taster		=99/1	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: rs35000; hg19: chr5-80277236;