7-33359319-C-G

Position:

• chr7-33359319-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198428.3(BBS9):​c.1693+1324C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.873 in 152,044 control chromosomes in the GnomAD database, including 58,262 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.87 (58262 hom., cov: 31)
• Consequence: BBS9 NM_198428.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.124

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BBS9	NM_198428.3	c.1693+1324C>G		intron_variant		ENST00000242067.11	NP_940820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BBS9	ENST00000242067.11	c.1693+1324C>G		intron_variant		1	NM_198428.3	ENSP00000242067.6

Frequencies

GnomAD3 genomes AF: 0.873 AC: 132667 AN: 151926 Hom.: 58194 Cov.: 31

Gnomad AFR AF: 0.966

Gnomad AMI AF: 0.814

Gnomad AMR AF: 0.878

Gnomad ASJ AF: 0.722

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.773

Gnomad FIN AF: 0.894

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.840

Gnomad OTH AF: 0.865

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.873 AC: 132799 AN: 152044 Hom.: 58262 Cov.: 31 AF XY: 0.875 AC XY: 65053 AN XY: 74334

Gnomad4 AFR AF: 0.966

Gnomad4 AMR AF: 0.878

Gnomad4 ASJ AF: 0.722

Gnomad4 EAS AF: 0.716

Gnomad4 SAS AF: 0.775

Gnomad4 FIN AF: 0.894

Gnomad4 NFE AF: 0.840

Gnomad4 OTH AF: 0.863

Alfa AF: 0.822 Hom.: 2570

Bravo AF: 0.876

Asia WGS AF: 0.734 AC: 2545 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.74
DANN	Benign	0.54

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: rs1008582; hg19: chr7-33398931;