5-81069982-T-C

Position:

• chr5-81069982-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006909.3(RASGRF2):​c.544-510T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 154,980 control chromosomes in the GnomAD database, including 6,121 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 0.27 (5988 hom., cov: 33)
  • Exomes 𝑓: 0.29 (133 hom.)
• Consequence: RASGRF2 NM_006909.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.133

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RASGRF2	NM_006909.3	c.544-510T>C		intron_variant		ENST00000265080.9	NP_008840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RASGRF2	ENST00000265080.9	c.544-510T>C		intron_variant		1	NM_006909.3	ENSP00000265080.4

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41211 AN: 152086 Hom.: 5991 Cov.: 33

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.266

GnomAD4 exome AF: 0.289 AC: 802 AN: 2776 Hom.: 133 Cov.: 0 AF XY: 0.287 AC XY: 422 AN XY: 1470

Gnomad4 AFR exome AF: 0.107

Gnomad4 AMR exome AF: 0.363

Gnomad4 ASJ exome AF: 0.400

Gnomad4 EAS exome AF: 0.115

Gnomad4 SAS exome AF: 0.252

Gnomad4 FIN exome AF: 0.222

Gnomad4 NFE exome AF: 0.291

Gnomad4 OTH exome AF: 0.232

GnomAD4 genome AF: 0.271 AC: 41213 AN: 152204 Hom.: 5988 Cov.: 33 AF XY: 0.271 AC XY: 20185 AN XY: 74410

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.358

Gnomad4 ASJ AF: 0.270

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.319

Gnomad4 NFE AF: 0.315

Gnomad4 OTH AF: 0.264

Alfa AF: 0.306 Hom.: 4434

Bravo AF: 0.271

Asia WGS AF: 0.200 AC: 698 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.6
DANN	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs26908; hg19: chr5-80365801;