chr7-33340986-G-T

Position:

• chr7-33340986-G-T

Variant summary

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

The ENST00000242067.11(BBS9):​c.1275+13G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 1,606,276 control chromosomes in the GnomAD database, including 65,673 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (5526 hom., cov: 31)
  • Exomes 𝑓: 0.28 (60147 hom.)
• Consequence: BBS9 ENST00000242067.11 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.538

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=-0.67).
• BP6: Variant 7-33340986-G-T is Benign according to our data. Variant chr7-33340986-G-T is described in ClinVar as [Benign]. Clinvar id is 263114.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-33340986-G-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BBS9	NM_198428.3	c.1275+13G>T		intron_variant		ENST00000242067.11	NP_940820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BBS9	ENST00000242067.11	c.1275+13G>T		intron_variant		1	NM_198428.3	ENSP00000242067	P3

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40100 AN: 151864 Hom.: 5525 Cov.: 31

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.0749

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.250

GnomAD3 exomes AF: 0.240 AC: 60175 AN: 250864 Hom.: 8036 AF XY: 0.243 AC XY: 32935 AN XY: 135586

Gnomad AFR exome AF: 0.241

Gnomad AMR exome AF: 0.141

Gnomad ASJ exome AF: 0.251

Gnomad EAS exome AF: 0.0714

Gnomad SAS exome AF: 0.209

Gnomad FIN exome AF: 0.273

Gnomad NFE exome AF: 0.297

Gnomad OTH exome AF: 0.260

GnomAD4 exome AF: 0.281 AC: 409159 AN: 1454294 Hom.: 60147 Cov.: 29 AF XY: 0.279 AC XY: 202325 AN XY: 724008

Gnomad4 AFR exome AF: 0.248

Gnomad4 AMR exome AF: 0.150

Gnomad4 ASJ exome AF: 0.249

Gnomad4 EAS exome AF: 0.0514

Gnomad4 SAS exome AF: 0.211

Gnomad4 FIN exome AF: 0.276

Gnomad4 NFE exome AF: 0.303

Gnomad4 OTH exome AF: 0.272

GnomAD4 genome AF: 0.264 AC: 40106 AN: 151982 Hom.: 5526 Cov.: 31 AF XY: 0.258 AC XY: 19182 AN XY: 74286

Gnomad4 AFR AF: 0.246

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.247

Gnomad4 EAS AF: 0.0749

Gnomad4 SAS AF: 0.215

Gnomad4 FIN AF: 0.268

Gnomad4 NFE AF: 0.304

Gnomad4 OTH AF: 0.247

Alfa AF: 0.282 Hom.: 1113

Bravo AF: 0.258

Asia WGS AF: 0.139 AC: 485 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

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. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Bardet-Biedl syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	7.2
DANN	Benign	0.79

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: rs11981364; hg19: chr7-33380598;