dbSNP rs17169881: BBS9:c.263+39A>G (chr7-33152890-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_198428.3(BBS9):c.263+39A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 1,599,346 control chromosomes in the GnomAD database, including 28,741 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2142 hom., cov: 31)

Exomes 𝑓: 0.19 ( 26599 hom. )

Consequence

BBS9
NM_198428.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0240

Publications

4 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: Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
BBS9-related 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 (BayesDel_noAF=-0.84).

BP6

Variant 7-33152890-A-G is Benign according to our data. Variant chr7-33152890-A-G is described in ClinVar as Benign. ClinVar VariationId is 263126.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198428.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BBS9	NM_198428.3	MANE Select	c.263+39A>G	intron	N/A	NP_940820.1	Q3SYG4-1
BBS9	NM_001348041.4		c.263+39A>G	intron	N/A	NP_001334970.1	A0A5F9ZH14
BBS9	NM_001348036.1		c.263+39A>G	intron	N/A	NP_001334965.1	Q3SYG4-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BBS9	ENST00000242067.11	TSL:1 MANE Select	c.263+39A>G	intron	N/A	ENSP00000242067.6	Q3SYG4-1
BBS9	ENST00000425508.6	TSL:1	c.128+39A>G	intron	N/A	ENSP00000405151.2	Q3SYG4-5
BBS9	ENST00000433714.5	TSL:1	n.263+39A>G	intron	N/A	ENSP00000412159.1	F8WCG5

Frequencies

GnomAD3 genomes

AF:

0.162

AC:

24598

AN:

152012

Hom.:

2137

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0976

Gnomad AMI

AF:

0.0844

Gnomad AMR

AF:

0.178

Gnomad ASJ

AF:

0.182

Gnomad EAS

AF:

0.155

Gnomad SAS

AF:

0.215

Gnomad FIN

AF:

0.208

Gnomad MID

AF:

0.196

Gnomad NFE

AF:

0.186

Gnomad OTH

AF:

0.178

GnomAD2 exomes

AF:

0.190

AC:

47691

AN:

250530

AF XY:

0.194

show subpopulations

Gnomad AFR exome

AF:

0.0965

Gnomad AMR exome

AF:

0.221

Gnomad ASJ exome

AF:

0.194

Gnomad EAS exome

AF:

0.167

Gnomad FIN exome

AF:

0.205

Gnomad NFE exome

AF:

0.184

Gnomad OTH exome

AF:

0.186

GnomAD4 exome

AF:

0.188

AC:

272463

AN:

1447216

Hom.:

26599

Cov.:

AF XY:

0.190

AC XY:

137210

AN XY:

720838

show subpopulations

African (AFR)

AF:

0.0943

AC:

3134

AN:

33240

American (AMR)

AF:

0.210

AC:

9399

AN:

44678

Ashkenazi Jewish (ASJ)

AF:

0.186

AC:

4829

AN:

26030

East Asian (EAS)

AF:

0.132

AC:

5226

AN:

39564

South Asian (SAS)

AF:

0.234

AC:

20065

AN:

85896

European-Finnish (FIN)

AF:

0.205

AC:

10894

AN:

53032

Middle Eastern (MID)

AF:

0.185

AC:

1048

AN:

5676

European-Non Finnish (NFE)

AF:

0.188

AC:

206814

AN:

1099204

Other (OTH)

AF:

0.185

AC:

11054

AN:

59896

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

10086

20172

30257

40343

50429

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7256

14512

21768

29024

36280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.162

AC:

24633

AN:

152130

Hom.:

2142

Cov.:

AF XY:

0.164

AC XY:

12170

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.0982

AC:

4076

AN:

41516

American (AMR)

AF:

0.178

AC:

2728

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.182

AC:

631

AN:

3470

East Asian (EAS)

AF:

0.154

AC:

797

AN:

5166

South Asian (SAS)

AF:

0.215

AC:

1035

AN:

4822

European-Finnish (FIN)

AF:

0.208

AC:

2202

AN:

10572

Middle Eastern (MID)

AF:

0.194

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.186

AC:

12649

AN:

67982

Other (OTH)

AF:

0.180

AC:

381

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1072

2144

3216

4288

5360

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

288

576

864

1152

1440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.178

Hom.:

913

Bravo

AF:

0.156

Asia WGS

AF:

0.201

AC:

698

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Bardet-Biedl syndrome 9 (1)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

(source)

DANN

Benign

0.77

PhyloP100

0.024

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over