Variant chr9-35749406-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001080496.3(RGP1):c.-22G>C variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0159 in 559,362 control chromosomes in the GnomAD database, including 573 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.043 ( 450 hom., cov: 32)

Exomes 𝑓: 0.0059 ( 123 hom. )

Consequence

RGP1
NM_001080496.3 splice_region

Scores

Splicing: ADA: 0.00009190

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.107

Variant links:

Genes affected

RGP1 (HGNC:21965): (RGP1 homolog, RAB6A GEF complex partner 1) Enables guanyl-nucleotide exchange factor activity and small GTPase binding activity. Involved in negative regulation of cellular protein catabolic process; positive regulation of GTPase activity; and retrograde transport, endosome to Golgi. Located in cytosol and plasma membrane. Part of Ric1-Rgp1 guanyl-nucleotide exchange factor complex. [provided by Alliance of Genome Resources, Apr 2022]

RGP1 links:

RGP1 (HGNC:):

RGP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 9-35749406-G-C is Benign according to our data. Variant chr9-35749406-G-C is described in ClinVar as [Benign]. Clinvar id is 1273691.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
RGP1	NM_001080496.3 linkuse as main transcript	c.-22G>C	splice_region_variant	1/9	ENST00000378078.5	NP_001073965.2	Q92546A8K0K1
RGP1	NM_001080496.3 linkuse as main transcript	c.-22G>C	5_prime_UTR_variant	1/9	ENST00000378078.5	NP_001073965.2	Q92546A8K0K1
RGP1	XR_007061382.1 linkuse as main transcript	n.120G>C	splice_region_variant, non_coding_transcript_exon_variant	1/12
RGP1	XR_007061383.1 linkuse as main transcript	n.120G>C	splice_region_variant, non_coding_transcript_exon_variant	1/12

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RGP1	ENST00000378078.5 linkuse as main transcript	c.-22G>C	splice_region_variant	1/9	1	NM_001080496.3	ENSP00000367318.4	Q92546
RGP1	ENST00000378078 linkuse as main transcript	c.-22G>C	5_prime_UTR_variant	1/9	1	NM_001080496.3	ENSP00000367318.4	Q92546
RGP1	ENST00000496906.1 linkuse as main transcript	n.116G>C	splice_region_variant, non_coding_transcript_exon_variant	1/9	5

Frequencies

GnomAD3 genomes

AF:

0.0424

AC:

6449

AN:

152142

Hom.:

450

Cov.:

show subpopulations

Gnomad AFR

AF:

0.145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0183

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00110

Gnomad OTH

AF:

0.0321

GnomAD3 exomes

AF:

0.0107

AC:

2651

AN:

246780

Hom.:

157

AF XY:

0.00811

AC XY:

1089

AN XY:

134236

show subpopulations

Gnomad AFR exome

AF:

0.145

Gnomad AMR exome

AF:

0.00839

Gnomad ASJ exome

AF:

0.00170

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000230

Gnomad FIN exome

AF:

0.0000950

Gnomad NFE exome

AF:

0.000920

Gnomad OTH exome

AF:

0.00701

GnomAD4 exome

AF:

0.00592

AC:

2412

AN:

407102

Hom.:

123

Cov.:

AF XY:

0.00448

AC XY:

1030

AN XY:

230124

show subpopulations

Gnomad4 AFR exome

AF:

0.146

Gnomad4 AMR exome

AF:

0.00866

Gnomad4 ASJ exome

AF:

0.00132

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000458

Gnomad4 FIN exome

AF:

0.000149

Gnomad4 NFE exome

AF:

0.000739

Gnomad4 OTH exome

AF:

0.0100

GnomAD4 genome

AF:

0.0425

AC:

6477

AN:

152260

Hom.:

450

Cov.:

AF XY:

0.0410

AC XY:

3054

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.145

Gnomad4 AMR

AF:

0.0182

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00109

Gnomad4 OTH

AF:

0.0317

Alfa

AF:

0.0130

Hom.:

Bravo

AF:

0.0478

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 07, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.5

DANN

Benign

0.70

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000092

dbscSNV1_RF

Benign

0.012

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over