Genetic Variant BBS9:p.Thr90Thr (chr7-33155644-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBP6_Very_Strong

The NM_001348038.3(BBS9):c.-4C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000396 in 1,591,236 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000055 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

BBS9
NM_001348038.3 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.188

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: 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant 7-33155644-C-T is Benign according to our data. Variant chr7-33155644-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 263128.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001348038.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BBS9	NM_198428.3	MANE Select	c.270C>T	p.Thr90Thr	synonymous	Exon 4 of 23	NP_940820.1	Q3SYG4-1
BBS9	NM_001348038.3		c.-4C>T		5_prime_UTR_premature_start_codon_gain	Exon 4 of 23	NP_001334967.1
BBS9	NM_001348039.3		c.-4C>T		5_prime_UTR_premature_start_codon_gain	Exon 4 of 22	NP_001334968.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BBS9	ENST00000242067.11	TSL:1 MANE Select	c.270C>T	p.Thr90Thr	synonymous	Exon 4 of 23	ENSP00000242067.6	Q3SYG4-1
BBS9	ENST00000425508.6	TSL:1	c.135C>T	p.Thr45Thr	synonymous	Exon 3 of 9	ENSP00000405151.2	Q3SYG4-5
BBS9	ENST00000433714.5	TSL:1	n.270C>T		non_coding_transcript_exon	Exon 4 of 24	ENSP00000412159.1	F8WCG5

Frequencies

GnomAD3 genomes

AF:

0.0000549

AC:

AN:

145774

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000100

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000136

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000218

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000153

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000603

AC:

AN:

248866

AF XY:

0.0000743

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.0000582

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000801

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000381

AC:

AN:

1445462

Hom.:

Cov.:

AF XY:

0.0000347

AC XY:

AN XY:

719786

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33220

American (AMR)

AF:

0.0000897

AC:

AN:

44592

Ashkenazi Jewish (ASJ)

AF:

0.0000385

AC:

AN:

25986

East Asian (EAS)

AF:

0.0000254

AC:

AN:

39346

South Asian (SAS)

AF:

0.000105

AC:

AN:

85706

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52734

Middle Eastern (MID)

AF:

0.000697

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

0.0000273

AC:

AN:

1098344

Other (OTH)

AF:

0.000100

AC:

AN:

59792

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.437

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000549

AC:

AN:

145774

Hom.:

Cov.:

AF XY:

0.0000423

AC XY:

AN XY:

70900

show subpopulations

African (AFR)

AF:

0.000100

AC:

AN:

39804

American (AMR)

AF:

0.000136

AC:

AN:

14702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3374

East Asian (EAS)

AF:

0.00

AC:

AN:

5036

South Asian (SAS)

AF:

0.000218

AC:

AN:

4582

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9912

Middle Eastern (MID)

AF:

0.00

AC:

AN:

304

European-Non Finnish (NFE)

AF:

0.0000153

AC:

AN:

65232

Other (OTH)

AF:

0.00

AC:

AN:

2002

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000117

Hom.:

Bravo

AF:

0.0000756

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (2)

Bardet-Biedl syndrome (1)

Bardet-Biedl syndrome 9 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Benign

0.68

PhyloP100

-0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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