5-81069068-T-C

Variant names:

• chr5-81069068-T-C
• rs26906
• NM_006909.3:c.543+889T>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.543+889T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 152,222 control chromosomes in the GnomAD database, including 56,463 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 0.86 (56463 hom., cov: 33)
• Consequence: RASGRF2 NM_006909.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0220
• Publications: 1 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 (NFE) allele frequency at 95% confidence interval = 0.92 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.543+889T>C		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.543+889T>C		intron	N/A	ENSP00000265080.4
	RASGRF2	ENST00000503795.1	TSL:1	n.543+889T>C		intron	N/A	ENSP00000421771.1
	RASGRF2	ENST00000638442.1	TSL:5	c.543+889T>C		intron	N/A	ENSP00000491428.1

Frequencies

GnomAD3 genomes AF: 0.857 AC: 130388 AN: 152104 Hom.: 56439 Cov.: 33

Gnomad AFR AF: 0.758

Gnomad AMI AF: 0.979

Gnomad AMR AF: 0.830

Gnomad ASJ AF: 0.870

Gnomad EAS AF: 0.675

Gnomad SAS AF: 0.809

Gnomad FIN AF: 0.938

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.926

Gnomad OTH AF: 0.864

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

GnomAD4 genome AF: 0.857 AC: 130451 AN: 152222 Hom.: 56463 Cov.: 33 AF XY: 0.855 AC XY: 63624 AN XY: 74424

African (AFR) AF: 0.758 AC: 31480 AN: 41522

American (AMR) AF: 0.829 AC: 12676 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.870 AC: 3020 AN: 3470

East Asian (EAS) AF: 0.675 AC: 3497 AN: 5178

South Asian (SAS) AF: 0.808 AC: 3894 AN: 4818

European-Finnish (FIN) AF: 0.938 AC: 9944 AN: 10604

Middle Eastern (MID) AF: 0.918 AC: 270 AN: 294

European-Non Finnish (NFE) AF: 0.926 AC: 62965 AN: 68024

Other (OTH) AF: 0.857 AC: 1814 AN: 2116

Alfa AF: 0.903 Hom.: 53501

Bravo AF: 0.846

Asia WGS AF: 0.711 AC: 2478 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	3.3
DANN	Benign	0.72
PhyloP100		-0.022
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: rs26906; hg19: chr5-80364887;