rs1020720

Positions:

• chr5-81176949-T-A

Variant summary

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

The NM_006909.3(RASGRF2):​c.2687-3226T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 151,854 control chromosomes in the GnomAD database, including 21,205 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 0.51 (21205 hom., cov: 31)
• Consequence: RASGRF2 NM_006909.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0100

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RASGRF2	NM_006909.3	c.2687-3226T>A		intron_variant		ENST00000265080.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RASGRF2	ENST00000265080.9	c.2687-3226T>A		intron_variant		1	NM_006909.3	P1
RASGRF2	ENST00000503795.1	c.2687-3226T>A		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.507 AC: 76986 AN: 151736 Hom.: 21192 Cov.: 31

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.537

Gnomad EAS AF: 0.816

Gnomad SAS AF: 0.503

Gnomad FIN AF: 0.600

Gnomad MID AF: 0.567

Gnomad NFE AF: 0.604

Gnomad OTH AF: 0.505

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

GnomAD4 genome AF: 0.507 AC: 77028 AN: 151854 Hom.: 21205 Cov.: 31 AF XY: 0.510 AC XY: 37823 AN XY: 74224

Gnomad4 AFR AF: 0.281

Gnomad4 AMR AF: 0.509

Gnomad4 ASJ AF: 0.537

Gnomad4 EAS AF: 0.817

Gnomad4 SAS AF: 0.504

Gnomad4 FIN AF: 0.600

Gnomad4 NFE AF: 0.604

Gnomad4 OTH AF: 0.508

Alfa AF: 0.542 Hom.: 2987

Bravo AF: 0.488

Asia WGS AF: 0.615 AC: 2136 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.33
DANN	Benign	0.78

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: rs1020720; hg19: chr5-80472768;