5-81069068-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.543+889T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 152,222 control chromosomes in the GnomAD database, including 56,463 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 0.86 (56463 hom., cov: 33)
• Consequence: RASGRF2 NM_006909.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0220

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RASGRF2	NM_006909.3	c.543+889T>C		intron_variant		ENST00000265080.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RASGRF2	ENST00000265080.9	c.543+889T>C		intron_variant		1	NM_006909.3	P1
RASGRF2	ENST00000503795.1	c.543+889T>C		intron_variant, NMD_transcript_variant		1
RASGRF2	ENST00000638442.1	c.543+889T>C		intron_variant		5
RASGRF2	ENST00000514946.1	n.434+889T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.857 AC: 130388 AN: 152104 Hom.: 56439 Cov.: 33

Gnomad AFR AF: 0.758

Gnomad AMI AF: 0.979

Gnomad AMR AF: 0.830

Gnomad ASJ AF: 0.870

Gnomad EAS AF: 0.675

Gnomad SAS AF: 0.809

Gnomad FIN AF: 0.938

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.926

Gnomad OTH AF: 0.864

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

GnomAD4 genome AF: 0.857 AC: 130451 AN: 152222 Hom.: 56463 Cov.: 33 AF XY: 0.855 AC XY: 63624 AN XY: 74424

Gnomad4 AFR AF: 0.758

Gnomad4 AMR AF: 0.829

Gnomad4 ASJ AF: 0.870

Gnomad4 EAS AF: 0.675

Gnomad4 SAS AF: 0.808

Gnomad4 FIN AF: 0.938

Gnomad4 NFE AF: 0.926

Gnomad4 OTH AF: 0.857

Alfa AF: 0.899 Hom.: 37443

Bravo AF: 0.846

Asia WGS AF: 0.711 AC: 2478 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	3.3
Dann	Benign	0.72

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: rs26906; hg19: chr5-80364887;