9-35751224-C-T

Variant names:

• chr9-35751224-C-T
• rs1570248
• NM_001080496.3:c.488-42C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080496.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGP1	NM_001080496.3	MANE Select	c.488-42C>T		intron	N/A	NP_001073965.2	Q92546

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGP1	ENST00000378078.5	TSL:1 MANE Select	c.488-42C>T		intron	N/A	ENSP00000367318.4	Q92546
	RGP1	ENST00000880976.1		c.488-42C>T		intron	N/A	ENSP00000551035.1
	RGP1	ENST00000931309.1		c.488-42C>T		intron	N/A	ENSP00000601368.1

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

GnomAD2 exomes AF: 0.674 AC: 166841 AN: 247678 AF XY: 0.673

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 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

African (AFR) AF: 0.724 AC: 24110 AN: 33320

American (AMR) AF: 0.650 AC: 28963 AN: 44530

Ashkenazi Jewish (ASJ) AF: 0.705 AC: 18289 AN: 25932

East Asian (EAS) AF: 0.790 AC: 31264 AN: 39594

South Asian (SAS) AF: 0.638 AC: 54815 AN: 85974

European-Finnish (FIN) AF: 0.635 AC: 33879 AN: 53324

Middle Eastern (MID) AF: 0.753 AC: 4325 AN: 5744

European-Non Finnish (NFE) AF: 0.662 AC: 733300 AN: 1106984

Other (OTH) AF: 0.674 AC: 40552 AN: 60148

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

African (AFR) AF: 0.723 AC: 29974 AN: 41444

American (AMR) AF: 0.647 AC: 9884 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.699 AC: 2424 AN: 3470

East Asian (EAS) AF: 0.827 AC: 4283 AN: 5176

South Asian (SAS) AF: 0.638 AC: 3065 AN: 4806

European-Finnish (FIN) AF: 0.624 AC: 6591 AN: 10562

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.667 AC: 45322 AN: 67936

Other (OTH) AF: 0.673 AC: 1421 AN: 2110

Alfa AF: 0.672 Hom.: 129232

Bravo AF: 0.687

Asia WGS AF: 0.647 AC: 2252 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.3
DANN	Benign	0.44
PhyloP100		-0.059
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1570248; hg19: chr9-35751221; COSMIC: COSV65240360; COSMIC: COSV65240360;