Variant 7-33129794-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BBS9	NM_198428.3 linkuse as main transcript	c.-259G>A		5_prime_UTR_variant	1/23	ENST00000242067.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BBS9	ENST00000242067.11 linkuse as main transcript	c.-259G>A		5_prime_UTR_variant	1/23	1	NM_198428.3	P3	Q3SYG4-1

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

Gnomad4 AFR exome

AF:

0.143

Gnomad4 AMR exome

AF:

0.125

Gnomad4 ASJ exome

AF:

0.250

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.167

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.210

Gnomad4 OTH exome

AF:

0.200

GnomAD4 genome

AF:

0.104

AC:

15863

AN:

152064

Hom.:

1147

Cov.:

AF XY:

0.101

AC XY:

7525

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.0276

Gnomad4 AMR

AF:

0.0808

Gnomad4 ASJ

AF:

0.0933

Gnomad4 EAS

AF:

0.00155

Gnomad4 SAS

AF:

0.0351

Gnomad4 FIN

AF:

0.160

Gnomad4 NFE

AF:

0.160

Gnomad4 OTH

AF:

0.0841

Alfa

AF:

0.126

Hom.:

244

Bravo

AF:

0.0930

Asia WGS

AF:

0.0170

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Bardet-Biedl syndrome 9

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

DANN

Benign

0.84

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over