rs888817

Positions:

• chr5-80961979-G-A

Variant summary

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

The ENST00000265080.9(RASGRF2):​c.288+953G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.678 in 152,106 control chromosomes in the GnomAD database, including 35,489 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 0.68 (35489 hom., cov: 32)
• Consequence: RASGRF2 ENST00000265080.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.377

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=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RASGRF2	NM_006909.3	c.288+953G>A		intron_variant		ENST00000265080.9	NP_008840.1
RASGRF2	XM_005248565.2	c.288+953G>A		intron_variant			XP_005248622.1
RASGRF2	XM_017009683.2	c.288+953G>A		intron_variant			XP_016865172.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RASGRF2	ENST00000265080.9	c.288+953G>A		intron_variant		1	NM_006909.3	ENSP00000265080	P1
RASGRF2	ENST00000503795.1	c.288+953G>A		intron_variant, NMD_transcript_variant		1		ENSP00000421771
RASGRF2	ENST00000638442.1	c.288+953G>A		intron_variant		5		ENSP00000491428

Frequencies

GnomAD3 genomes AF: 0.678 AC: 103015 AN: 151988 Hom.: 35440 Cov.: 32

Gnomad AFR AF: 0.788

Gnomad AMI AF: 0.694

Gnomad AMR AF: 0.633

Gnomad ASJ AF: 0.739

Gnomad EAS AF: 0.504

Gnomad SAS AF: 0.721

Gnomad FIN AF: 0.608

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.638

Gnomad OTH AF: 0.664

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

GnomAD4 genome AF: 0.678 AC: 103117 AN: 152106 Hom.: 35489 Cov.: 32 AF XY: 0.676 AC XY: 50254 AN XY: 74328

Gnomad4 AFR AF: 0.789

Gnomad4 AMR AF: 0.632

Gnomad4 ASJ AF: 0.739

Gnomad4 EAS AF: 0.504

Gnomad4 SAS AF: 0.722

Gnomad4 FIN AF: 0.608

Gnomad4 NFE AF: 0.638

Gnomad4 OTH AF: 0.662

Alfa AF: 0.650 Hom.: 52996

Bravo AF: 0.684

Asia WGS AF: 0.593 AC: 2060 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	9.0
DANN	Benign	0.81

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: rs888817; hg19: chr5-80257798;