dbSNP rs10486527: BBS9:c.1275+88T>C (chr7-33341061-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_198428.3(BBS9):c.1275+88T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 1,146,312 control chromosomes in the GnomAD database, including 41,763 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.26 ( 5534 hom., cov: 31)

Exomes 𝑓: 0.26 ( 36229 hom. )

Consequence

BBS9
NM_198428.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.309

Publications

6 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 7-33341061-T-C is Benign according to our data. Variant chr7-33341061-T-C is described in ClinVar as Benign. ClinVar VariationId is 1237819.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.301 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.1275+88T>C	intron	N/A	NP_940820.1	Q3SYG4-1
BBS9	NM_001348041.4		c.1275+88T>C	intron	N/A	NP_001334970.1	A0A5F9ZH14
BBS9	NM_001348036.1		c.1275+88T>C	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.1275+88T>C	intron	N/A	ENSP00000242067.6	Q3SYG4-1
BBS9	ENST00000433714.5	TSL:1	n.1275+88T>C	intron	N/A	ENSP00000412159.1	F8WCG5
BBS9	ENST00000942912.1		c.1401+88T>C	intron	N/A	ENSP00000612971.1

Frequencies

GnomAD3 genomes

AF:

0.264

AC:

40104

AN:

151776

Hom.:

5533

Cov.:

show subpopulations

Gnomad AFR

AF:

0.246

Gnomad AMI

AF:

0.442

Gnomad AMR

AF:

0.208

Gnomad ASJ

AF:

0.247

Gnomad EAS

AF:

0.0742

Gnomad SAS

AF:

0.217

Gnomad FIN

AF:

0.267

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.304

Gnomad OTH

AF:

0.250

GnomAD4 exome

AF:

0.263

AC:

261284

AN:

994418

Hom.:

36229

AF XY:

0.262

AC XY:

134681

AN XY:

514118

show subpopulations

African (AFR)

AF:

0.239

AC:

5829

AN:

24340

American (AMR)

AF:

0.147

AC:

6222

AN:

42320

Ashkenazi Jewish (ASJ)

AF:

0.245

AC:

5628

AN:

22970

East Asian (EAS)

AF:

0.0489

AC:

1811

AN:

37028

South Asian (SAS)

AF:

0.211

AC:

15949

AN:

75630

European-Finnish (FIN)

AF:

0.269

AC:

13050

AN:

48526

Middle Eastern (MID)

AF:

0.260

AC:

1258

AN:

4836

European-Non Finnish (NFE)

AF:

0.288

AC:

199891

AN:

694318

Other (OTH)

AF:

0.262

AC:

11646

AN:

44450

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

8175

16350

24525

32700

40875

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5024

10048

15072

20096

25120

<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:

0.264

AC:

40112

AN:

151894

Hom.:

5534

Cov.:

AF XY:

0.258

AC XY:

19182

AN XY:

74244

show subpopulations

African (AFR)

AF:

0.246

AC:

10193

AN:

41420

American (AMR)

AF:

0.208

AC:

3176

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.247

AC:

855

AN:

3468

East Asian (EAS)

AF:

0.0742

AC:

384

AN:

5178

South Asian (SAS)

AF:

0.217

AC:

1046

AN:

4810

European-Finnish (FIN)

AF:

0.267

AC:

2820

AN:

10568

Middle Eastern (MID)

AF:

0.241

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.304

AC:

20644

AN:

67890

Other (OTH)

AF:

0.247

AC:

520

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1466

2932

4398

5864

7330

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

414

828

1242

1656

2070

<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:

0.176

Hom.:

363

Bravo

AF:

0.258

Asia WGS

AF:

0.141

AC:

493

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

3.7

(source)

DANN

Benign

0.57

PhyloP100

-0.31

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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