rs1445078208

Positions:

• chr7-33177472-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_198428.3(BBS9):​c.329-6C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00054 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BBS9 NM_198428.3 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00009510
• Clinical Significance: Likely benign criteria provided, single submitter B:3
• Conservation: PhyloP100: -0.156

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 7-33177472-C-T is Benign according to our data. Variant chr7-33177472-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 462971.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-33177472-C-T is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BBS9	NM_198428.3	c.329-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000242067.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BBS9	ENST00000242067.11	c.329-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_198428.3	P3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 76 AN: 140414 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.000263

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000704

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000223

Gnomad FIN AF: 0.00352

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000545

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00131 AC: 1736 AN: 1321058 Hom.: 0 Cov.: 27 AF XY: 0.00131 AC XY: 867 AN XY: 660694

Gnomad4 AFR exome AF: 0.00519

Gnomad4 AMR exome AF: 0.0144

Gnomad4 ASJ exome AF: 0.00242

Gnomad4 EAS exome AF: 0.000428

Gnomad4 SAS exome AF: 0.00442

Gnomad4 FIN exome AF: 0.000555

Gnomad4 NFE exome AF: 0.000524

Gnomad4 OTH exome AF: 0.00150

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000541 AC: 76 AN: 140514 Hom.: 0 Cov.: 32 AF XY: 0.000485 AC XY: 33 AN XY: 67980

Gnomad4 AFR AF: 0.000262

Gnomad4 AMR AF: 0.0000703

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000224

Gnomad4 FIN AF: 0.00352

Gnomad4 NFE AF: 0.000545

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0139 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:2

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

Bardet-Biedl syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 28, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	2.4
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000095
dbscSNV1_RF	Benign	0.010
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: rs1445078208; hg19: chr7-33217084; COSMIC: COSV54164970; COSMIC: COSV54164970;