rs153226

Variant names:

• chr5-81075096-T-C
• rs153226
• NM_006909.3:c.887+1644T>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.887+1644T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 152,044 control chromosomes in the GnomAD database, including 10,561 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 0.37 (10561 hom., cov: 32)
• Consequence: RASGRF2 NM_006909.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14
• Publications: 5 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=-0.57).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.425 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.887+1644T>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.887+1644T>C		intron	N/A	ENSP00000265080.4
	RASGRF2	ENST00000503795.1	TSL:1	n.887+1644T>C		intron	N/A	ENSP00000421771.1
	RASGRF2	ENST00000638442.1	TSL:5	c.887+1644T>C		intron	N/A	ENSP00000491428.1

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55912 AN: 151926 Hom.: 10541 Cov.: 32

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.345

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

GnomAD4 genome AF: 0.368 AC: 55966 AN: 152044 Hom.: 10561 Cov.: 32 AF XY: 0.368 AC XY: 27325 AN XY: 74316

African (AFR) AF: 0.330 AC: 13687 AN: 41476

American (AMR) AF: 0.434 AC: 6631 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 1313 AN: 3460

East Asian (EAS) AF: 0.133 AC: 687 AN: 5174

South Asian (SAS) AF: 0.366 AC: 1761 AN: 4808

European-Finnish (FIN) AF: 0.407 AC: 4296 AN: 10556

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.389 AC: 26413 AN: 67974

Other (OTH) AF: 0.341 AC: 717 AN: 2104

Alfa AF: 0.383 Hom.: 22390

Bravo AF: 0.371

Asia WGS AF: 0.252 AC: 878 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	6.9
DANN	Benign	0.97
PhyloP100		1.1
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: rs153226; hg19: chr5-80370915;