Genetic Variant BBS9:c.-259G>A (chr7-33129794-G-A) – 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.-259G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,500 control chromosomes in the GnomAD database, including 1,159 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.10 ( 1147 hom., cov: 31)

Exomes 𝑓: 0.19 ( 12 hom. )

Consequence

BBS9
NM_198428.3 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.02

Publications

3 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=-0.82).

BP6

Variant 7-33129794-G-A is Benign according to our data. Variant chr7-33129794-G-A is described in ClinVar as Benign. ClinVar VariationId is 360055.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.158 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.-259G>A	5_prime_UTR	Exon 1 of 23	NP_940820.1	Q3SYG4-1
BBS9	NM_001348041.4		c.-259G>A	5_prime_UTR	Exon 1 of 23	NP_001334970.1	A0A5F9ZH14
BBS9	NM_001348043.3		c.-259G>A	5_prime_UTR	Exon 1 of 23	NP_001334972.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BBS9	ENST00000242067.11	TSL:1 MANE Select	c.-259G>A	5_prime_UTR	Exon 1 of 23	ENSP00000242067.6	Q3SYG4-1
BBS9	ENST00000433714.5	TSL:1	n.-259G>A	non_coding_transcript_exon	Exon 1 of 24	ENSP00000412159.1	F8WCG5
BBS9	ENST00000433714.5	TSL:1	n.-259G>A	5_prime_UTR	Exon 1 of 24	ENSP00000412159.1	F8WCG5

Frequencies

GnomAD3 genomes

AF:

0.104

AC:

15863

AN:

151946

Hom.:

1147

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0277

Gnomad AMI

AF:

0.230

Gnomad AMR

AF:

0.0809

Gnomad ASJ

AF:

0.0933

Gnomad EAS

AF:

0.00155

Gnomad SAS

AF:

0.0351

Gnomad FIN

AF:

0.160

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.160

Gnomad OTH

AF:

0.0850

GnomAD4 exome

AF:

0.195

AC:

AN:

436

Hom.:

Cov.:

AF XY:

0.200

AC XY:

AN XY:

360

show subpopulations

African (AFR)

AF:

0.143

AC:

AN:

American (AMR)

AF:

0.125

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.167

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.210

AC:

AN:

362

Other (OTH)

AF:

0.200

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.526

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

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:

0.104

AC:

15863

AN:

152064

Hom.:

1147

Cov.:

AF XY:

0.101

AC XY:

7525

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.0276

AC:

1147

AN:

41526

American (AMR)

AF:

0.0808

AC:

1235

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.0933

AC:

324

AN:

3472

East Asian (EAS)

AF:

0.00155

AC:

AN:

5158

South Asian (SAS)

AF:

0.0351

AC:

169

AN:

4810

European-Finnish (FIN)

AF:

0.160

AC:

1691

AN:

10552

Middle Eastern (MID)

AF:

0.0782

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.160

AC:

10878

AN:

67948

Other (OTH)

AF:

0.0841

AC:

178

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

657

1314

1971

2628

3285

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

186

372

558

744

930

<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:

0.123

Hom.:

244

Bravo

AF:

0.0930

Asia WGS

AF:

0.0170

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Bardet-Biedl syndrome 9 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

(source)

DANN

Benign

0.84

PhyloP100

1.0

PromoterAI

0.013

Neutral

(source)

Mutation Taster

=300/0

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