9-35749547-T-C

Position:

• chr9-35749547-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001080496.3(RGP1):​c.-20+139T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0199 in 680,676 control chromosomes in the GnomAD database, including 1,096 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.058 (797 hom., cov: 32)
  • Exomes 𝑓: 0.0089 (299 hom.)
• Consequence: RGP1 NM_001080496.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.77

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 9-35749547-T-C is Benign according to our data. Variant chr9-35749547-T-C is described in ClinVar as [Benign]. Clinvar id is 1288609.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGP1	NM_001080496.3	c.-20+139T>C		intron_variant		ENST00000378078.5	NP_001073965.2
RGP1	XR_007061382.1	n.122+139T>C		intron_variant
RGP1	XR_007061383.1	n.122+139T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGP1	ENST00000378078.5	c.-20+139T>C		intron_variant		1	NM_001080496.3	ENSP00000367318.4
RGP1	ENST00000496906.1	n.118+139T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0578 AC: 8778 AN: 151948 Hom.: 791 Cov.: 32

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0231

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00236

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00272

Gnomad OTH AF: 0.0407

GnomAD4 exome AF: 0.00894 AC: 4728 AN: 528610 Hom.: 299 AF XY: 0.00713 AC XY: 2038 AN XY: 285982

Gnomad4 AFR exome AF: 0.192

Gnomad4 AMR exome AF: 0.0109

Gnomad4 ASJ exome AF: 0.000606

Gnomad4 EAS exome AF: 0.0000332

Gnomad4 SAS exome AF: 0.000596

Gnomad4 FIN exome AF: 0.00428

Gnomad4 NFE exome AF: 0.00258

Gnomad4 OTH exome AF: 0.0170

GnomAD4 genome AF: 0.0579 AC: 8809 AN: 152066 Hom.: 797 Cov.: 32 AF XY: 0.0559 AC XY: 4154 AN XY: 74354

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.0230

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000831

Gnomad4 FIN AF: 0.00236

Gnomad4 NFE AF: 0.00272

Gnomad4 OTH AF: 0.0402

Alfa AF: 0.0300 Hom.: 57

Bravo AF: 0.0653

Asia WGS AF: 0.0150 AC: 53 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 18, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.6
DANN	Benign	0.55

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

Other links and lift over

dbSNP: rs113827764; hg19: chr9-35749544;