7-33359319-C-G

Variant names:

• chr7-33359319-C-G
• rs1008582
• NM_198428.3:c.1693+1324C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• Bardet-Biedl syndrome 9

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
• BBS9-related ciliopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Bardet-Biedl syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198428.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBS9	NM_198428.3	MANE Select	c.1693+1324C>G		intron	N/A	NP_940820.1	Q3SYG4-1
	BBS9	NM_001348041.4		c.1693+1324C>G		intron	N/A	NP_001334970.1	A0A5F9ZH14
	BBS9	NM_001348036.1		c.1693+1324C>G		intron	N/A	NP_001334965.1	Q3SYG4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBS9	ENST00000242067.11	TSL:1 MANE Select	c.1693+1324C>G		intron	N/A	ENSP00000242067.6	Q3SYG4-1
	BBS9	ENST00000434373.3	TSL:1	c.391+1324C>G		intron	N/A	ENSP00000388114.1	H7BZ69
	BBS9	ENST00000433714.5	TSL:1	n.*454+1324C>G		intron	N/A	ENSP00000412159.1	F8WCG5

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

African (AFR) AF: 0.966 AC: 40151 AN: 41560

American (AMR) AF: 0.878 AC: 13405 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.722 AC: 2497 AN: 3460

East Asian (EAS) AF: 0.716 AC: 3706 AN: 5174

South Asian (SAS) AF: 0.775 AC: 3734 AN: 4820

European-Finnish (FIN) AF: 0.894 AC: 9474 AN: 10594

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.840 AC: 57024 AN: 67866

Other (OTH) AF: 0.863 AC: 1816 AN: 2104

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.74
DANN	Benign	0.54
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1008582; hg19: chr7-33398931;