9-5732483-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_020829.4(RIC1):c.812+4T>C variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 1,588,990 control chromosomes in the GnomAD database, including 166,264 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.39 (13586 hom., cov: 32)
  • Exomes 𝑓: 0.45 (152678 hom.)
• Consequence: RIC1 NM_020829.4 splice_donor_region, intron
• Scores: Splicing: ADA: 0.009878
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.14

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=-0.32).
• BP6: Variant 9-5732483-T-C is Benign according to our data. Variant chr9-5732483-T-C is described in ClinVar as [Benign]. Clinvar id is 1300069.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIC1	NM_020829.4	c.812+4T>C		splice_donor_region_variant, intron_variant		ENST00000414202.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIC1	ENST00000414202.7	c.812+4T>C		splice_donor_region_variant, intron_variant		5	NM_020829.4	P1

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59702 AN: 151876 Hom.: 13582 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.852

Gnomad SAS AF: 0.597

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.389

GnomAD3 exomes AF: 0.494 AC: 118219 AN: 239322 Hom.: 31740 AF XY: 0.498 AC XY: 64372 AN XY: 129380

Gnomad AFR exome AF: 0.179

Gnomad AMR exome AF: 0.543

Gnomad ASJ exome AF: 0.442

Gnomad EAS exome AF: 0.867

Gnomad SAS exome AF: 0.585

Gnomad FIN exome AF: 0.502

Gnomad NFE exome AF: 0.446

Gnomad OTH exome AF: 0.477

GnomAD4 exome AF: 0.451 AC: 647926 AN: 1437000 Hom.: 152678 Cov.: 26 AF XY: 0.455 AC XY: 325430 AN XY: 715262

Gnomad4 AFR exome AF: 0.168

Gnomad4 AMR exome AF: 0.532

Gnomad4 ASJ exome AF: 0.435

Gnomad4 EAS exome AF: 0.850

Gnomad4 SAS exome AF: 0.576

Gnomad4 FIN exome AF: 0.504

Gnomad4 NFE exome AF: 0.430

Gnomad4 OTH exome AF: 0.453

GnomAD4 genome AF: 0.393 AC: 59714 AN: 151990 Hom.: 13586 Cov.: 32 AF XY: 0.404 AC XY: 30029 AN XY: 74292

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.480

Gnomad4 ASJ AF: 0.431

Gnomad4 EAS AF: 0.852

Gnomad4 SAS AF: 0.597

Gnomad4 FIN AF: 0.492

Gnomad4 NFE AF: 0.434

Gnomad4 OTH AF: 0.396

Alfa AF: 0.403 Hom.: 8420

Bravo AF: 0.382

Asia WGS AF: 0.681 AC: 2363 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Catifa syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
Cadd	Benign	20
Dann	Benign	0.96

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0099
dbscSNV1_RF	Benign	0.29
SpliceAI score (max)		0.12		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: rs7850299; hg19: chr9-5732483;