rs34999

Variant names:

• chr5-80981226-C-T
• rs34999
• NM_006909.3:c.288+20200C>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.288+20200C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 151,920 control chromosomes in the GnomAD database, including 33,236 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 0.66 (33236 hom., cov: 32)
• Consequence: RASGRF2 NM_006909.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.251
• Publications: 6 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 (EAS) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASGRF2	NM_006909.3	c.288+20200C>T		intron_variant	Intron 1 of 26	ENST00000265080.9	NP_008840.1
RASGRF2	XM_047417464.1	c.-85+4425C>T		intron_variant	Intron 1 of 26		XP_047273420.1
RASGRF2	XM_005248565.2	c.288+20200C>T		intron_variant	Intron 1 of 18		XP_005248622.1
RASGRF2	XM_017009683.2	c.288+20200C>T		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+20200C>T		intron_variant	Intron 1 of 26	1	NM_006909.3	ENSP00000265080.4
RASGRF2	ENST00000503795.1	n.288+20200C>T		intron_variant	Intron 1 of 27	1		ENSP00000421771.1
RASGRF2	ENST00000638442.1	c.288+20200C>T		intron_variant	Intron 1 of 9	5		ENSP00000491428.1

Frequencies

GnomAD3 genomes AF: 0.660 AC: 100250 AN: 151802 Hom.: 33220 Cov.: 32

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.584

Gnomad AMR AF: 0.677

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.763

Gnomad SAS AF: 0.650

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.653

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

GnomAD4 genome AF: 0.660 AC: 100318 AN: 151920 Hom.: 33236 Cov.: 32 AF XY: 0.658 AC XY: 48832 AN XY: 74244

African (AFR) AF: 0.662 AC: 27390 AN: 41398

American (AMR) AF: 0.677 AC: 10335 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.616 AC: 2135 AN: 3468

East Asian (EAS) AF: 0.764 AC: 3946 AN: 5168

South Asian (SAS) AF: 0.648 AC: 3116 AN: 4806

European-Finnish (FIN) AF: 0.615 AC: 6472 AN: 10528

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.659 AC: 44808 AN: 67962

Other (OTH) AF: 0.653 AC: 1380 AN: 2114

Alfa AF: 0.665 Hom.: 47091

Bravo AF: 0.668

Asia WGS AF: 0.716 AC: 2489 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.81
DANN	Benign	0.66
PhyloP100		-0.25
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: rs34999; hg19: chr5-80277045; COSMIC: COSV54139255;