rs73101660

Positions:

• chr7-33349217-T-A
• chr7-33349217-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_198428.3(BBS9):​c.1432+47T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 1,358,850 control chromosomes in the GnomAD database, including 28,948 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2849 hom., cov: 32)
  • Exomes 𝑓: 0.20 (26099 hom.)
• Consequence: BBS9 NM_198428.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.96

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 7-33349217-T-A is Benign according to our data. Variant chr7-33349217-T-A is described in ClinVar as [Benign]. Clinvar id is 263118.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BBS9	NM_198428.3	c.1432+47T>A		intron_variant		ENST00000242067.11	NP_940820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BBS9	ENST00000242067.11	c.1432+47T>A		intron_variant		1	NM_198428.3	ENSP00000242067.6

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28068 AN: 152038 Hom.: 2848 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.0752

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.162

GnomAD3 exomes AF: 0.159 AC: 39600 AN: 248450 Hom.: 3919 AF XY: 0.158 AC XY: 21238 AN XY: 134360

Gnomad AFR exome AF: 0.170

Gnomad AMR exome AF: 0.101

Gnomad ASJ exome AF: 0.142

Gnomad EAS exome AF: 0.00203

Gnomad SAS exome AF: 0.0780

Gnomad FIN exome AF: 0.200

Gnomad NFE exome AF: 0.217

Gnomad OTH exome AF: 0.176

GnomAD4 exome AF: 0.201 AC: 242998 AN: 1206694 Hom.: 26099 Cov.: 17 AF XY: 0.197 AC XY: 120693 AN XY: 612888

Gnomad4 AFR exome AF: 0.179

Gnomad4 AMR exome AF: 0.105

Gnomad4 ASJ exome AF: 0.142

Gnomad4 EAS exome AF: 0.000813

Gnomad4 SAS exome AF: 0.0803

Gnomad4 FIN exome AF: 0.207

Gnomad4 NFE exome AF: 0.229

Gnomad4 OTH exome AF: 0.191

GnomAD4 genome AF: 0.185 AC: 28075 AN: 152156 Hom.: 2849 Cov.: 32 AF XY: 0.179 AC XY: 13326 AN XY: 74380

Gnomad4 AFR AF: 0.174

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.00289

Gnomad4 SAS AF: 0.0752

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.161

Alfa AF: 0.121 Hom.: 290

Bravo AF: 0.178

Asia WGS AF: 0.0550 AC: 191 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.018
DANN	Benign	0.27

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: rs73101660; hg19: chr7-33388829;