rs11773504

Variant summary

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

The NM_198428.3(BBS9):c.1363G>A(p.Ala455Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 1,610,110 control chromosomes in the GnomAD database, including 34,089 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A455V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.18 ( 2564 hom., cov: 32)

Exomes 𝑓: 0.21 ( 31525 hom. )

Consequence

BBS9
NM_198428.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.38

Variant links:

Genes affected

BBS9 (HGNC:30000): (Bardet-Biedl syndrome 9) This gene is downregulated by parathyroid hormone in osteoblastic cells, and therefore is thought to be involved in parathyroid hormone action in bones. The exact function of this gene has not yet been determined. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jan 2017]

BBS9 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 (MetaRNN=8.8375807E-4).

BP6

Variant 7-33349101-G-A is Benign according to our data. Variant chr7-33349101-G-A is described in ClinVar as [Benign]. Clinvar id is 263117.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-33349101-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BBS9	NM_198428.3 linkuse as main transcript	c.1363G>A	p.Ala455Thr	missense_variant	13/23	ENST00000242067.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BBS9	ENST00000242067.11 linkuse as main transcript	c.1363G>A	p.Ala455Thr	missense_variant	13/23	1	NM_198428.3	P3	Q3SYG4-1

Frequencies

GnomAD3 genomes

AF:

0.177

AC:

26979

AN:

152020

Hom.:

2562

Cov.:

show subpopulations

Gnomad AFR

AF:

0.117

Gnomad AMI

AF:

0.0857

Gnomad AMR

AF:

0.185

Gnomad ASJ

AF:

0.179

Gnomad EAS

AF:

0.197

Gnomad SAS

AF:

0.206

Gnomad FIN

AF:

0.211

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.205

Gnomad OTH

AF:

0.182

GnomAD3 exomes

AF:

0.205

AC:

51549

AN:

251226

Hom.:

5524

AF XY:

0.207

AC XY:

28168

AN XY:

135808

show subpopulations

Gnomad AFR exome

AF:

0.120

Gnomad AMR exome

AF:

0.226

Gnomad ASJ exome

AF:

0.186

Gnomad EAS exome

AF:

0.210

Gnomad SAS exome

AF:

0.233

Gnomad FIN exome

AF:

0.215

Gnomad NFE exome

AF:

0.203

Gnomad OTH exome

AF:

0.192

GnomAD4 exome

AF:

0.205

AC:

298906

AN:

1457972

Hom.:

31525

Cov.:

AF XY:

0.206

AC XY:

149616

AN XY:

725512

show subpopulations

Gnomad4 AFR exome

AF:

0.112

Gnomad4 AMR exome

AF:

0.215

Gnomad4 ASJ exome

AF:

0.179

Gnomad4 EAS exome

AF:

0.171

Gnomad4 SAS exome

AF:

0.230

Gnomad4 FIN exome

AF:

0.213

Gnomad4 NFE exome

AF:

0.207

Gnomad4 OTH exome

AF:

0.201

GnomAD4 genome

AF:

0.177

AC:

26997

AN:

152138

Hom.:

2564

Cov.:

AF XY:

0.177

AC XY:

13187

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.117

Gnomad4 AMR

AF:

0.185

Gnomad4 ASJ

AF:

0.179

Gnomad4 EAS

AF:

0.197

Gnomad4 SAS

AF:

0.205

Gnomad4 FIN

AF:

0.211

Gnomad4 NFE

AF:

0.205

Gnomad4 OTH

AF:

0.185

Alfa

AF:

0.189

Hom.:

1509

Bravo

AF:

0.173

TwinsUK

AF:

0.219

AC:

811

ALSPAC

AF:

0.214

AC:

823

ESP6500AA

AF:

0.126

AC:

556

ESP6500EA

AF:

0.201

AC:

1727

ExAC

AF:

0.204

AC:

24791

Asia WGS

AF:

0.203

AC:

708

AN:

3478

EpiCase

AF:

0.203

EpiControl

AF:

0.198

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Bardet-Biedl syndrome 1

Benign:2

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Sep 21, 2015	- -

Bardet-Biedl syndrome 9

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Bardet-Biedl syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.38

Cadd

Benign

Dann

Benign

0.93

DEOGEN2

Benign

0.027

T;.;.;.

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.095

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.61

T;T;T;T

MetaRNN

Benign

0.00088

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.20

N;N;N;N

MutationTaster

Benign

1.0

P;P;P;P;P

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.44

N;N;N;N

REVEL

Benign

0.045

Sift

Benign

0.23

T;T;T;T

Sift4G

Benign

0.34

T;T;T;T

Polyphen

0.0010

B;B;B;.

Vest4

0.066

MPC

0.097

ClinPred

0.0075

GERP RS

3.2

Varity_R

0.091

gMVP

0.19

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