9-5693377-C-G

Variant summary

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

The NM_020829.4(RIC1):c.332+3339C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 151,910 control chromosomes in the GnomAD database, including 8,980 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 0.32 (8980 hom., cov: 32)
• Consequence: RIC1 NM_020829.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.22

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIC1	NM_020829.4	c.332+3339C>G		intron_variant		ENST00000414202.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIC1	ENST00000414202.7	c.332+3339C>G		intron_variant		5	NM_020829.4	P1
RIC1	ENST00000251879.10	c.332+3339C>G		intron_variant		1
RIC1	ENST00000545641.5	c.117+3339C>G		intron_variant		1
RIC1	ENST00000418622.7	c.332+3339C>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48366 AN: 151792 Hom.: 8971 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.357

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.622

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.317

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.319 AC: 48388 AN: 151910 Hom.: 8980 Cov.: 32 AF XY: 0.326 AC XY: 24228 AN XY: 74224

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.358

Gnomad4 ASJ AF: 0.372

Gnomad4 EAS AF: 0.621

Gnomad4 SAS AF: 0.520

Gnomad4 FIN AF: 0.400

Gnomad4 NFE AF: 0.368

Gnomad4 OTH AF: 0.322

Alfa AF: 0.349 Hom.: 1219

Bravo AF: 0.308

Asia WGS AF: 0.499 AC: 1737 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.73
Dann	Benign	0.62

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: rs10491558; hg19: chr9-5693377;