rs9791555

Variant names:

• chr7-33205516-A-G
• rs9791555
• NM_198428.3:c.442+27925A>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.442+27925A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0851 in 152,196 control chromosomes in the GnomAD database, including 590 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 0.085 (590 hom., cov: 32)
• Consequence: BBS9 NM_198428.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33
• Publications: 2 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: G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BBS9	NM_198428.3	c.442+27925A>G		intron_variant	Intron 5 of 22	ENST00000242067.11	NP_940820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BBS9	ENST00000242067.11	c.442+27925A>G		intron_variant	Intron 5 of 22	1	NM_198428.3	ENSP00000242067.6

Frequencies

GnomAD3 genomes AF: 0.0851 AC: 12941 AN: 152078 Hom.: 590 Cov.: 32

Gnomad AFR AF: 0.0832

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.0632

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.0756

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.0812

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0876

Gnomad OTH AF: 0.0965

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

GnomAD4 genome AF: 0.0851 AC: 12947 AN: 152196 Hom.: 590 Cov.: 32 AF XY: 0.0848 AC XY: 6311 AN XY: 74416

African (AFR) AF: 0.0831 AC: 3451 AN: 41530

American (AMR) AF: 0.0631 AC: 965 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 362 AN: 3468

East Asian (EAS) AF: 0.0757 AC: 392 AN: 5176

South Asian (SAS) AF: 0.136 AC: 656 AN: 4816

European-Finnish (FIN) AF: 0.0812 AC: 861 AN: 10598

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0876 AC: 5957 AN: 68004

Other (OTH) AF: 0.0955 AC: 202 AN: 2116

Alfa AF: 0.0878 Hom.: 318

Bravo AF: 0.0855

Asia WGS AF: 0.0870 AC: 303 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.9
DANN	Benign	0.71
PhyloP100		1.3
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: rs9791555; hg19: chr7-33245128;