9-131603630-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001377935.1(RAPGEF1):​c.2412+331T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.856 in 152,168 control chromosomes in the GnomAD database, including 55,984 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 ( 55984 hom., cov: 31)

Consequence

RAPGEF1
NM_001377935.1 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.138
Variant links:
Genes affected
RAPGEF1 (HGNC:4568): (Rap guanine nucleotide exchange factor 1) This gene encodes a human guanine nucleotide exchange factor. It transduces signals from CRK by binding the SH3 domain of CRK, and activating several members of the Ras family of GTPases. This signaling cascade that may be involved in apoptosis, integrin-mediated signal transduction, and cell transformation. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some variants has not been determined. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.926 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RAPGEF1NM_001377935.1 linkc.2412+331T>C intron_variant Intron 14 of 26 ENST00000683357.1 NP_001364864.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RAPGEF1ENST00000683357.1 linkc.2412+331T>C intron_variant Intron 14 of 26 NM_001377935.1 ENSP00000508246.1 A0A804HL87
RAPGEF1ENST00000372189.7 linkc.1855-1481T>C intron_variant Intron 11 of 23 1 ENSP00000361263.2 Q13905-1

Frequencies

GnomAD3 genomes
AF:
0.856
AC:
130132
AN:
152050
Hom.:
55923
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.934
Gnomad AMI
AF:
0.853
Gnomad AMR
AF:
0.847
Gnomad ASJ
AF:
0.820
Gnomad EAS
AF:
0.795
Gnomad SAS
AF:
0.833
Gnomad FIN
AF:
0.869
Gnomad MID
AF:
0.829
Gnomad NFE
AF:
0.817
Gnomad OTH
AF:
0.849
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.856
AC:
130252
AN:
152168
Hom.:
55984
Cov.:
31
AF XY:
0.858
AC XY:
63838
AN XY:
74400
show subpopulations
Gnomad4 AFR
AF:
0.934
Gnomad4 AMR
AF:
0.847
Gnomad4 ASJ
AF:
0.820
Gnomad4 EAS
AF:
0.795
Gnomad4 SAS
AF:
0.834
Gnomad4 FIN
AF:
0.869
Gnomad4 NFE
AF:
0.817
Gnomad4 OTH
AF:
0.847
Alfa
AF:
0.840
Hom.:
8669
Bravo
AF:
0.857
Asia WGS
AF:
0.839
AC:
2921
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
2.0
DANN
Benign
0.42

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: rs7034356; hg19: chr9-134479017; API