9-35751224-C-T

Position:

• chr9-35751224-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080496.3(RGP1):​c.488-42C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.668 in 1,607,544 control chromosomes in the GnomAD database, including 359,339 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 0.68 (35470 hom., cov: 31)
  • Exomes 𝑓: 0.67 (323869 hom.)
• Consequence: RGP1 NM_001080496.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0590

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGP1	NM_001080496.3	c.488-42C>T		intron_variant		ENST00000378078.5	NP_001073965.2
RGP1	XR_007061382.1	n.629-42C>T		intron_variant
RGP1	XR_007061383.1	n.629-42C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGP1	ENST00000378078.5	c.488-42C>T		intron_variant		1	NM_001080496.3	ENSP00000367318.4
RGP1	ENST00000496906.1	n.723-42C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.682 AC: 103529 AN: 151876 Hom.: 35425 Cov.: 31

Gnomad AFR AF: 0.723

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.646

Gnomad ASJ AF: 0.699

Gnomad EAS AF: 0.827

Gnomad SAS AF: 0.637

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.667

Gnomad OTH AF: 0.677

GnomAD3 exomes AF: 0.674 AC: 166841 AN: 247678 Hom.: 56647 AF XY: 0.673 AC XY: 90385 AN XY: 134334

Gnomad AFR exome AF: 0.728

Gnomad AMR exome AF: 0.647

Gnomad ASJ exome AF: 0.710

Gnomad EAS exome AF: 0.835

Gnomad SAS exome AF: 0.633

Gnomad FIN exome AF: 0.633

Gnomad NFE exome AF: 0.664

Gnomad OTH exome AF: 0.679

GnomAD4 exome AF: 0.666 AC: 969497 AN: 1455550 Hom.: 323869 Cov.: 33 AF XY: 0.666 AC XY: 481791 AN XY: 723584

Gnomad4 AFR exome AF: 0.724

Gnomad4 AMR exome AF: 0.650

Gnomad4 ASJ exome AF: 0.705

Gnomad4 EAS exome AF: 0.790

Gnomad4 SAS exome AF: 0.638

Gnomad4 FIN exome AF: 0.635

Gnomad4 NFE exome AF: 0.662

Gnomad4 OTH exome AF: 0.674

GnomAD4 genome AF: 0.682 AC: 103626 AN: 151994 Hom.: 35470 Cov.: 31 AF XY: 0.679 AC XY: 50456 AN XY: 74284

Gnomad4 AFR AF: 0.723

Gnomad4 AMR AF: 0.647

Gnomad4 ASJ AF: 0.699

Gnomad4 EAS AF: 0.827

Gnomad4 SAS AF: 0.638

Gnomad4 FIN AF: 0.624

Gnomad4 NFE AF: 0.667

Gnomad4 OTH AF: 0.673

Alfa AF: 0.671 Hom.: 53264

Bravo AF: 0.687

Asia WGS AF: 0.647 AC: 2252 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.3
DANN	Benign	0.44
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs1570248; hg19: chr9-35751221; COSMIC: COSV65240360; COSMIC: COSV65240360;