chr5-81069496-G-A

Variant names:

• chr5-81069496-G-A
• rs26907
• NM_006909.3:c.544-996G>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.544-996G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,194 control chromosomes in the GnomAD database, including 1,912 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 0.15 (1912 hom., cov: 33)
• Consequence: RASGRF2 NM_006909.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.606
• Publications: 14 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 (AMR) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASGRF2	NM_006909.3	c.544-996G>A		intron_variant	Intron 3 of 26	ENST00000265080.9	NP_008840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASGRF2	ENST00000265080.9	c.544-996G>A		intron_variant	Intron 3 of 26	1	NM_006909.3	ENSP00000265080.4
RASGRF2	ENST00000503795.1	n.544-996G>A		intron_variant	Intron 3 of 27	1		ENSP00000421771.1
RASGRF2	ENST00000638442.1	c.544-996G>A		intron_variant	Intron 3 of 9	5		ENSP00000491428.1
RASGRF2	ENST00000514946.1	n.435-996G>A		intron_variant	Intron 3 of 4	5

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23350 AN: 152076 Hom.: 1913 Cov.: 33

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.153 AC: 23350 AN: 152194 Hom.: 1912 Cov.: 33 AF XY: 0.155 AC XY: 11525 AN XY: 74430

African (AFR) AF: 0.127 AC: 5256 AN: 41530

American (AMR) AF: 0.244 AC: 3730 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 467 AN: 3468

East Asian (EAS) AF: 0.113 AC: 587 AN: 5188

South Asian (SAS) AF: 0.123 AC: 595 AN: 4818

European-Finnish (FIN) AF: 0.184 AC: 1953 AN: 10590

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.150 AC: 10215 AN: 67990

Other (OTH) AF: 0.147 AC: 310 AN: 2114

Alfa AF: 0.153 Hom.: 8207

Bravo AF: 0.163

Asia WGS AF: 0.119 AC: 417 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	12
DANN	Benign	0.76
PhyloP100		0.61
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: rs26907; hg19: chr5-80365315;