rs17727583

Positions:

• chr7-33533934-A-C
• chr7-33533934-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_198428.3(BBS9):​c.2299-20A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0122 in 1,613,594 control chromosomes in the GnomAD database, including 149 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0098 (13 hom., cov: 32)
  • Exomes 𝑓: 0.012 (136 hom.)
• Consequence: BBS9 NM_198428.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.0740

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 7-33533934-A-C is Benign according to our data. Variant chr7-33533934-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 263124.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-33533934-A-C is described in Lovd as [Likely_benign]. Variant chr7-33533934-A-C is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00981 (1495/152338) while in subpopulation NFE AF= 0.0144 (980/68022). AF 95% confidence interval is 0.0137. There are 13 homozygotes in gnomad4. There are 717 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BBS9	NM_198428.3	c.2299-20A>C		intron_variant		ENST00000242067.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BBS9	ENST00000242067.11	c.2299-20A>C		intron_variant		1	NM_198428.3	P3

Frequencies

GnomAD3 genomes AF: 0.00982 AC: 1495 AN: 152220 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.00265

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.0143

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00188

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0144

Gnomad OTH AF: 0.0148

GnomAD3 exomes AF: 0.00923 AC: 2320 AN: 251404 Hom.: 18 AF XY: 0.00929 AC XY: 1262 AN XY: 135878

Gnomad AFR exome AF: 0.00197

Gnomad AMR exome AF: 0.00720

Gnomad ASJ exome AF: 0.0138

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00242

Gnomad FIN exome AF: 0.00402

Gnomad NFE exome AF: 0.0146

Gnomad OTH exome AF: 0.0137

GnomAD4 exome AF: 0.0125 AC: 18202 AN: 1461256 Hom.: 136 Cov.: 30 AF XY: 0.0122 AC XY: 8903 AN XY: 726988

Gnomad4 AFR exome AF: 0.00209

Gnomad4 AMR exome AF: 0.00762

Gnomad4 ASJ exome AF: 0.0134

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00259

Gnomad4 FIN exome AF: 0.00449

Gnomad4 NFE exome AF: 0.0145

Gnomad4 OTH exome AF: 0.0128

GnomAD4 genome AF: 0.00981 AC: 1495 AN: 152338 Hom.: 13 Cov.: 32 AF XY: 0.00962 AC XY: 717 AN XY: 74504

Gnomad4 AFR AF: 0.00265

Gnomad4 AMR AF: 0.0142

Gnomad4 ASJ AF: 0.0130

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00186

Gnomad4 FIN AF: 0.00188

Gnomad4 NFE AF: 0.0144

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.00654 Hom.: 2

Bravo AF: 0.0108

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Bardet-Biedl syndrome 1 Benign:4

Benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	Oct 09, 2014	- -
Likely benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	May 31, 2017	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	Apr 19, 2017	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Bardet-Biedl syndrome 9 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Aug 04, 2021

- -

Bardet-Biedl syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.6
DANN	Benign	0.72

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

Other links and lift over

dbSNP: rs17727583; hg19: chr7-33573546;