dbSNP rs10486541: BBS9:c.2633-7475G>A (chr7-33627702-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001348041.4(BBS9):c.2633-7475G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 152,134 control chromosomes in the GnomAD database, including 4,208 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.21 ( 4208 hom., cov: 33)

Consequence

BBS9
NM_001348041.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0820

Publications

1 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, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
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

new If you want to explore the variant's impact on the transcript NM_001348041.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001348041.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBS9	NM_001348041.4		c.2633-7475G>A		intron	N/A	NP_001334970.1	A0A5F9ZH14
	BBS9	NM_001362679.1		c.2522-7475G>A		intron	N/A	NP_001349608.1	A0A5F9ZHE7

Ensembl Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
BBS9	ENST00000673056.1	c.2633-7475G>A	intron	N/A	ENSP00000499989.1	A0A5F9ZH14
BBS9	ENST00000671952.1	c.2522-7475G>A	intron	N/A	ENSP00000500239.1	A0A5F9ZHE7
BBS9	ENST00000672453.1	n.2476+21970G>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.213

AC:

32307

AN:

152016

Hom.:

4202

Cov.:

show subpopulations

Gnomad AFR

AF:

0.339

Gnomad AMI

AF:

0.229

Gnomad AMR

AF:

0.143

Gnomad ASJ

AF:

0.235

Gnomad EAS

AF:

0.444

Gnomad SAS

AF:

0.226

Gnomad FIN

AF:

0.103

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.148

Gnomad OTH

AF:

0.212

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.212

AC:

32325

AN:

152134

Hom.:

4208

Cov.:

AF XY:

0.210

AC XY:

15602

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.339

AC:

14063

AN:

41478

American (AMR)

AF:

0.143

AC:

2192

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.235

AC:

815

AN:

3468

East Asian (EAS)

AF:

0.444

AC:

2289

AN:

5160

South Asian (SAS)

AF:

0.224

AC:

1079

AN:

4810

European-Finnish (FIN)

AF:

0.103

AC:

1090

AN:

10608

Middle Eastern (MID)

AF:

0.231

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.148

AC:

10077

AN:

67990

Other (OTH)

AF:

0.209

AC:

443

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1259

2518

3777

5036

6295

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

336

672

1008

1344

1680

<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:

0.169

Hom.:

4097

Bravo

AF:

0.221

Asia WGS

AF:

0.296

AC:

1027

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.0

(source)

DANN

Benign

0.82

PhyloP100

0.082

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over