Variant chr9-5732483-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

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, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.14

Variant links:

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]

RIC1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 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_multiple_submitters_no_conflicts, 2 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 linkuse as main transcript	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 linkuse as main transcript	c.812+4T>C		splice_donor_region_variant, intron_variant		5	NM_020829.4	P1	Q4ADV7-1

Frequencies

GnomAD3 genomes

AF:

0.393

AC:

59702

AN:

151876

Hom.:

13582

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.455

AC XY:

325430

AN XY:

715262

show subpopulations

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.:

AF XY:

0.404

AC XY:

30029

AN XY:

74292

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Catifa syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over