Genetic Variant BBS9:p.Ile617Val (chr7-33383725-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_198428.3(BBS9):c.1849A>G(p.Ile617Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,906 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I617L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

BBS9
NM_198428.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.75

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1781806).

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	HGVSp	Effect	Exon Rank	Protein
BBS9	NM_198428.3	MANE Select	c.1849A>G	p.Ile617Val	missense	Exon 18 of 23	NP_940820.1
BBS9	NM_001348041.4		c.1849A>G	p.Ile617Val	missense	Exon 18 of 23	NP_001334970.1
BBS9	NM_001348036.1		c.1849A>G	p.Ile617Val	missense	Exon 18 of 23	NP_001334965.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
BBS9	ENST00000242067.11	TSL:1 MANE Select	c.1849A>G	p.Ile617Val	missense	Exon 18 of 23	ENSP00000242067.6
BBS9	ENST00000434373.3	TSL:1	c.547A>G	p.Ile183Val	missense	Exon 7 of 11	ENSP00000388114.1
BBS9	ENST00000433714.5	TSL:1	n.*610A>G		non_coding_transcript_exon	Exon 19 of 24	ENSP00000412159.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459906

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726110

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33464

American (AMR)

AF:

0.00

AC:

AN:

44596

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26038

East Asian (EAS)

AF:

0.00

AC:

AN:

39656

South Asian (SAS)

AF:

0.00

AC:

AN:

85918

European-Finnish (FIN)

AF:

0.0000188

AC:

AN:

53298

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5580

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111048

Other (OTH)

AF:

0.00

AC:

AN:

60308

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.018

Eigen

Uncertain

0.21

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.0027

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.76

PhyloP100

5.8

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.15

REVEL

Benign

0.056

Sift

Benign

0.60

Sift4G

Benign

0.66

Polyphen

0.015

Vest4

0.18

MutPred

0.26

Loss of catalytic residue at L618 (P = 0.4062)

MVP

0.31

MPC

0.059

ClinPred

0.71

GERP RS

6.1

Varity_R

0.091

gMVP

0.082

Mutation Taster

=98/2

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over