Variant 9-5762533-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020829.4(RIC1):c.1993-8A>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 1,610,362 control chromosomes in the GnomAD database, including 117,467 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 9636 hom., cov: 32)

Exomes 𝑓: 0.38 ( 107831 hom. )

Consequence

RIC1
NM_020829.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00005038

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.455

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:

ERMP1 (HGNC:23703): (endoplasmic reticulum metallopeptidase 1) Predicted to enable metal ion binding activity and metalloexopeptidase activity. Involved in cellular response to oxidative stress. Acts upstream of or within endoplasmic reticulum unfolded protein response. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ERMP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 9-5762533-A-C is Benign according to our data. Variant chr9-5762533-A-C is described in ClinVar as [Benign]. Clinvar id is 1300070.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIC1	NM_020829.4 linkuse as main transcript	c.1993-8A>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000414202.7	NP_065880.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIC1	ENST00000414202.7 linkuse as main transcript	c.1993-8A>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_020829.4	ENSP00000416696	P1	Q4ADV7-1

Frequencies

GnomAD3 genomes

AF:

0.343

AC:

52106

AN:

151882

Hom.:

9623

Cov.:

show subpopulations

Gnomad AFR

AF:

0.225

Gnomad AMI

AF:

0.380

Gnomad AMR

AF:

0.361

Gnomad ASJ

AF:

0.368

Gnomad EAS

AF:

0.589

Gnomad SAS

AF:

0.494

Gnomad FIN

AF:

0.384

Gnomad MID

AF:

0.427

Gnomad NFE

AF:

0.373

Gnomad OTH

AF:

0.350

GnomAD3 exomes

AF:

0.404

AC:

100509

AN:

248546

Hom.:

21273

AF XY:

0.408

AC XY:

54809

AN XY:

134198

show subpopulations

Gnomad AFR exome

AF:

0.224

Gnomad AMR exome

AF:

0.427

Gnomad ASJ exome

AF:

0.363

Gnomad EAS exome

AF:

0.588

Gnomad SAS exome

AF:

0.477

Gnomad FIN exome

AF:

0.389

Gnomad NFE exome

AF:

0.382

Gnomad OTH exome

AF:

0.396

GnomAD4 exome

AF:

0.380

AC:

554104

AN:

1458362

Hom.:

107831

Cov.:

AF XY:

0.383

AC XY:

278050

AN XY:

725364

show subpopulations

Gnomad4 AFR exome

AF:

0.217

Gnomad4 AMR exome

AF:

0.421

Gnomad4 ASJ exome

AF:

0.355

Gnomad4 EAS exome

AF:

0.610

Gnomad4 SAS exome

AF:

0.476

Gnomad4 FIN exome

AF:

0.392

Gnomad4 NFE exome

AF:

0.368

Gnomad4 OTH exome

AF:

0.377

GnomAD4 genome

AF:

0.343

AC:

52163

AN:

152000

Hom.:

9636

Cov.:

AF XY:

0.348

AC XY:

25877

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.225

Gnomad4 AMR

AF:

0.362

Gnomad4 ASJ

AF:

0.368

Gnomad4 EAS

AF:

0.589

Gnomad4 SAS

AF:

0.495

Gnomad4 FIN

AF:

0.384

Gnomad4 NFE

AF:

0.373

Gnomad4 OTH

AF:

0.356

Alfa

AF:

0.355

Hom.:

8230

Bravo

AF:

0.336

Asia WGS

AF:

0.493

AC:

1713

AN:

3478

EpiCase

AF:

0.383

EpiControl

AF:

0.383

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

-0.83

CADD

Benign

8.2

DANN

Benign

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000050

dbscSNV1_RF

Benign

0.0020

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

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