rs378645

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_006909.3(RASGRF2):​c.289-3354A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00307 in 152,318 control chromosomes in the GnomAD database, including 5 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 0.0031 ( 5 hom., cov: 32)

Consequence

RASGRF2
NM_006909.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.347
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BS2
High AC in GnomAd4 at 468 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RASGRF2NM_006909.3 linkuse as main transcriptc.289-3354A>G intron_variant ENST00000265080.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RASGRF2ENST00000265080.9 linkuse as main transcriptc.289-3354A>G intron_variant 1 NM_006909.3 P1
RASGRF2ENST00000503795.1 linkuse as main transcriptc.289-3354A>G intron_variant, NMD_transcript_variant 1
RASGRF2ENST00000638442.1 linkuse as main transcriptc.289-3354A>G intron_variant 5
RASGRF2ENST00000514946.1 linkuse as main transcriptn.180-3354A>G intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
AF:
0.00307
AC:
468
AN:
152200
Hom.:
5
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000844
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00864
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000942
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00428
Gnomad OTH
AF:
0.00431
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.00307
AC:
468
AN:
152318
Hom.:
5
Cov.:
32
AF XY:
0.00311
AC XY:
232
AN XY:
74486
show subpopulations
Gnomad4 AFR
AF:
0.000842
Gnomad4 AMR
AF:
0.00863
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000942
Gnomad4 NFE
AF:
0.00428
Gnomad4 OTH
AF:
0.00427
Alfa
AF:
0.00286
Hom.:
0
Bravo
AF:
0.00342
Asia WGS
AF:
0.000580
AC:
2
AN:
3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.75
CADD
Benign
13
DANN
Benign
0.90

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs378645; hg19: chr5-80335342; API