Variant 3-15073869-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_022340.4(RBSN):c.2268C>T(p.Cys756Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00304 in 1,613,944 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0022 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0031 ( 15 hom. )

Consequence

RBSN
NM_022340.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.623

Variant links:

Genes affected

RBSN (HGNC:20759): (rabenosyn, RAB effector) This gene encodes a protein that belongs to the FYVE zinc finger family of proteins. The encoded protein interacts with Ras-related proteins that regulate membrane trafficking. A missense mutation in this gene is associated with a defect in the early endocytic pathway. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014]

RBSN links:

ENSG00000289750 (HGNC:):

ENSG00000289750 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 3-15073869-G-A is Benign according to our data. Variant chr3-15073869-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 718312.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.623 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBSN	NM_022340.4 linkuse as main transcript	c.2268C>T	p.Cys756Cys	synonymous_variant	14/14	ENST00000253699.7	NP_071735.2	Q9H1K0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RBSN	ENST00000253699.7 linkuse as main transcript	c.2268C>T	p.Cys756Cys	synonymous_variant	14/14	1	NM_022340.4	ENSP00000253699.3	Q9H1K0-1
RBSN	ENST00000476527.6 linkuse as main transcript	c.2268C>T	p.Cys756Cys	synonymous_variant	13/13	2		ENSP00000422551.1	Q9H1K0-1
ENSG00000289750	ENST00000698784.1 linkuse as main transcript	n.1683C>T		non_coding_transcript_exon_variant	8/9
ENSG00000289750	ENST00000698785.1 linkuse as main transcript	n.2879C>T		non_coding_transcript_exon_variant	14/17

Frequencies

GnomAD3 genomes

AF:

0.00217

AC:

330

AN:

152030

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000459

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00583

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00319

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00276

AC:

693

AN:

251144

Hom.:

AF XY:

0.00304

AC XY:

413

AN XY:

135724

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00150

Gnomad ASJ exome

AF:

0.0123

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00379

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00329

Gnomad OTH exome

AF:

0.00342

GnomAD4 exome

AF:

0.00313

AC:

4578

AN:

1461796

Hom.:

Cov.:

AF XY:

0.00320

AC XY:

2324

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.000508

Gnomad4 AMR exome

AF:

0.00161

Gnomad4 ASJ exome

AF:

0.0113

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00458

Gnomad4 FIN exome

AF:

0.000338

Gnomad4 NFE exome

AF:

0.00317

Gnomad4 OTH exome

AF:

0.00359

GnomAD4 genome

AF:

0.00218

AC:

332

AN:

152148

Hom.:

Cov.:

AF XY:

0.00199

AC XY:

148

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.000458

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.0121

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00625

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00319

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00314

Hom.:

Bravo

AF:

0.00224

Asia WGS

AF:

0.00202

AC:

AN:

3476

EpiCase

AF:

0.00436

EpiControl

AF:

0.00415

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2023	RBSN: BP4, BP7 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

0.63

DANN

Benign

0.48

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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