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GeneBe

9-131596338-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001377935.1(RAPGEF1):c.2649G>A(p.Gly883=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00675 in 1,613,944 control chromosomes in the GnomAD database, including 52 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0049 ( 5 hom., cov: 32)
Exomes 𝑓: 0.0069 ( 47 hom. )

Consequence

RAPGEF1
NM_001377935.1 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.45
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 -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 9-131596338-C-T is Benign according to our data. Variant chr9-131596338-C-T is described in ClinVar as [Benign]. Clinvar id is 710212.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.45 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 748 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RAPGEF1NM_001377935.1 linkuse as main transcriptc.2649G>A p.Gly883= synonymous_variant 17/27 ENST00000683357.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RAPGEF1ENST00000683357.1 linkuse as main transcriptc.2649G>A p.Gly883= synonymous_variant 17/27 NM_001377935.1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00492
AC:
748
AN:
152134
Hom.:
5
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000990
Gnomad AMI
AF:
0.00110
Gnomad AMR
AF:
0.00406
Gnomad ASJ
AF:
0.000576
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00394
Gnomad FIN
AF:
0.00716
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00791
Gnomad OTH
AF:
0.00431
GnomAD3 exomes
AF:
0.00491
AC:
1224
AN:
249254
Hom.:
7
AF XY:
0.00519
AC XY:
702
AN XY:
135244
show subpopulations
Gnomad AFR exome
AF:
0.000903
Gnomad AMR exome
AF:
0.00162
Gnomad ASJ exome
AF:
0.000894
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00405
Gnomad FIN exome
AF:
0.00538
Gnomad NFE exome
AF:
0.00781
Gnomad OTH exome
AF:
0.00363
GnomAD4 exome
AF:
0.00695
AC:
10152
AN:
1461692
Hom.:
47
Cov.:
31
AF XY:
0.00691
AC XY:
5021
AN XY:
727126
show subpopulations
Gnomad4 AFR exome
AF:
0.000717
Gnomad4 AMR exome
AF:
0.00208
Gnomad4 ASJ exome
AF:
0.00107
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00431
Gnomad4 FIN exome
AF:
0.00536
Gnomad4 NFE exome
AF:
0.00811
Gnomad4 OTH exome
AF:
0.00509
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00491
AC:
748
AN:
152252
Hom.:
5
Cov.:
32
AF XY:
0.00505
AC XY:
376
AN XY:
74430
show subpopulations
Gnomad4 AFR
AF:
0.000987
Gnomad4 AMR
AF:
0.00405
Gnomad4 ASJ
AF:
0.000576
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00394
Gnomad4 FIN
AF:
0.00716
Gnomad4 NFE
AF:
0.00791
Gnomad4 OTH
AF:
0.00426
Alfa
AF:
0.00672
Hom.:
1
Bravo
AF:
0.00433
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.00703
EpiControl
AF:
0.00753

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJul 30, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.55
Cadd
Benign
2.0
Dann
Benign
0.56
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.8

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs35658906; hg19: chr9-134471725; API