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GeneBe

9-5742888-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_020829.4(RIC1):c.921A>G(p.Gly307=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00359 in 1,612,310 control chromosomes in the GnomAD database, including 171 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.018 ( 84 hom., cov: 32)
Exomes 𝑓: 0.0021 ( 87 hom. )

Consequence

RIC1
NM_020829.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.23
Variant links:
Genes affected
RIC1 (HGNC:17686): (RIC1 homolog, RAB6A GEF complex partner 1) Enables guanyl-nucleotide exchange factor activity and small GTPase binding activity. Involved in several processes, including positive regulation of GTPase activity; regulation of extracellular matrix constituent secretion; and retrograde transport, endosome to Golgi. Located in cytosol and membrane. Part of Ric1-Rgp1 guanyl-nucleotide exchange factor complex. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 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=-0.49).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 9-5742888-A-G is Benign according to our data. Variant chr9-5742888-A-G is described in ClinVar as [Benign]. Clinvar id is 776406.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=1.23 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0595 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RIC1NM_020829.4 linkuse as main transcriptc.921A>G p.Gly307= synonymous_variant 9/26 ENST00000414202.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RIC1ENST00000414202.7 linkuse as main transcriptc.921A>G p.Gly307= synonymous_variant 9/265 NM_020829.4 P1Q4ADV7-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0177
AC:
2692
AN:
151896
Hom.:
84
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0611
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00767
Gnomad ASJ
AF:
0.00202
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000208
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00318
Gnomad NFE
AF:
0.000250
Gnomad OTH
AF:
0.0115
GnomAD3 exomes
AF:
0.00491
AC:
1231
AN:
250776
Hom.:
33
AF XY:
0.00364
AC XY:
493
AN XY:
135510
show subpopulations
Gnomad AFR exome
AF:
0.0620
Gnomad AMR exome
AF:
0.00398
Gnomad ASJ exome
AF:
0.00348
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000282
Gnomad OTH exome
AF:
0.00278
GnomAD4 exome
AF:
0.00210
AC:
3071
AN:
1460306
Hom.:
87
Cov.:
31
AF XY:
0.00181
AC XY:
1314
AN XY:
726488
show subpopulations
Gnomad4 AFR exome
AF:
0.0664
Gnomad4 AMR exome
AF:
0.00459
Gnomad4 ASJ exome
AF:
0.00307
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000163
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000230
Gnomad4 OTH exome
AF:
0.00464
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0179
AC:
2714
AN:
152004
Hom.:
84
Cov.:
32
AF XY:
0.0173
AC XY:
1283
AN XY:
74282
show subpopulations
Gnomad4 AFR
AF:
0.0615
Gnomad4 AMR
AF:
0.00760
Gnomad4 ASJ
AF:
0.00202
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000250
Gnomad4 OTH
AF:
0.0118
Alfa
AF:
0.00849
Hom.:
21
Bravo
AF:
0.0207
Asia WGS
AF:
0.00520
AC:
18
AN:
3478
EpiCase
AF:
0.000709
EpiControl
AF:
0.000593

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 testingInvitaeApr 20, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.49
Cadd
Benign
9.9
Dann
Benign
0.70

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: rs75782093; hg19: chr9-5742888; API