rs61764067

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_198428.3(BBS9):c.1246G>A(p.Val416Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.004 in 1,613,512 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0039 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0040 ( 34 hom. )

Consequence

BBS9
NM_198428.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -2.25

Publications

12 publications found

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 Gene-Disease associations (from GenCC):

Bardet-Biedl syndrome 9
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
ciliopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Bardet-Biedl syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

BBS9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0039181113).

BP6

Variant 7-33340944-G-A is Benign according to our data. Variant chr7-33340944-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 96647.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00389 (592/152152) while in subpopulation EAS AF = 0.0155 (80/5174). AF 95% confidence interval is 0.0127. There are 4 homozygotes in GnomAd4. There are 295 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BBS9	NM_198428.3 link	c.1246G>A	p.Val416Met	missense_variant	Exon 11 of 23	ENST00000242067.11	NP_940820.1	Q3SYG4-1A0A090N8P4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BBS9	ENST00000242067.11 link	c.1246G>A	p.Val416Met	missense_variant	Exon 11 of 23	1	NM_198428.3	ENSP00000242067.6		Q3SYG4-1

Frequencies

GnomAD3 genomes

AF:

0.00389

AC:

592

AN:

152034

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000676

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00957

Gnomad ASJ

AF:

0.00980

Gnomad EAS

AF:

0.0154

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00746

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00310

Gnomad OTH

AF:

0.00288

GnomAD2 exomes

AF:

0.00607

AC:

1526

AN:

251382

AF XY:

0.00551

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.0175

Gnomad ASJ exome

AF:

0.0109

Gnomad EAS exome

AF:

0.0132

Gnomad FIN exome

AF:

0.00619

Gnomad NFE exome

AF:

0.00295

Gnomad OTH exome

AF:

0.00766

GnomAD4 exome

AF:

0.00401

AC:

5866

AN:

1461360

Hom.:

Cov.:

AF XY:

0.00395

AC XY:

2869

AN XY:

726968

show subpopulations

African (AFR)

AF:

0.000627

AC:

AN:

33472

American (AMR)

AF:

0.0180

AC:

803

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00961

AC:

251

AN:

26124

East Asian (EAS)

AF:

0.0244

AC:

968

AN:

39666

South Asian (SAS)

AF:

0.00155

AC:

134

AN:

86242

European-Finnish (FIN)

AF:

0.00669

AC:

357

AN:

53358

Middle Eastern (MID)

AF:

0.000694

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00276

AC:

3063

AN:

1111634

Other (OTH)

AF:

0.00439

AC:

265

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

295

590

886

1181

1476

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00389

AC:

592

AN:

152152

Hom.:

Cov.:

AF XY:

0.00397

AC XY:

295

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.000674

AC:

AN:

41524

American (AMR)

AF:

0.00955

AC:

146

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00980

AC:

AN:

3470

East Asian (EAS)

AF:

0.0155

AC:

AN:

5174

South Asian (SAS)

AF:

0.00166

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00746

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00310

AC:

211

AN:

67980

Other (OTH)

AF:

0.00237

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

112

140

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00359

Hom.:

Bravo

AF:

0.00413

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00256

AC:

ExAC

AF:

0.00556

AC:

675

Asia WGS

AF:

0.00808

AC:

AN:

3478

EpiCase

AF:

0.00289

EpiControl

AF:

0.00219

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Aug 29, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 21, 2016

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Bardet-Biedl syndrome 1

Benign:2

Jan 27, 2015

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 12, 2017

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Bardet-Biedl syndrome 9

Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Bardet-Biedl syndrome

Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.51

CADD

Benign

0.011

(source)

DANN

Benign

0.77

DEOGEN2

Benign

0.056

T;.;.;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0059

LIST_S2

Benign

0.78

T;T;T;T

MetaRNN

Benign

0.0039

T;T;T;T

MetaSVM

Benign

-0.77

MutationAssessor

Benign

0.69

N;N;N;N

PhyloP100

-2.2

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.62

N;N;N;N

REVEL

Benign

0.15

Sift

Benign

0.26

T;T;T;T

Sift4G

Benign

0.25

T;T;T;T

Polyphen

0.0070

B;B;B;.

Vest4

0.11

MVP

0.43

MPC

0.064

ClinPred

0.0070

GERP RS

-9.0

Varity_R

0.058

gMVP

0.12

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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rs61764067

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over