rs7799346

Variant names:

• chr7-33272408-G-A
• rs7799346
• NM_198428.3:c.703-604G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198428.3(BBS9):​c.703-604G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0822 in 152,142 control chromosomes in the GnomAD database, including 548 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 0.082 (548 hom., cov: 32)
• Consequence: BBS9 NM_198428.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.185
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BBS9	NM_198428.3	c.703-604G>A		intron_variant	Intron 7 of 22	ENST00000242067.11	NP_940820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BBS9	ENST00000242067.11	c.703-604G>A		intron_variant	Intron 7 of 22	1	NM_198428.3	ENSP00000242067.6

Frequencies

GnomAD3 genomes AF: 0.0822 AC: 12498 AN: 152024 Hom.: 548 Cov.: 32

Gnomad AFR AF: 0.0750

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.0616

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.0710

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.0811

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0872

Gnomad OTH AF: 0.0904

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

GnomAD4 genome AF: 0.0822 AC: 12504 AN: 152142 Hom.: 548 Cov.: 32 AF XY: 0.0819 AC XY: 6090 AN XY: 74390

African (AFR) AF: 0.0749 AC: 3112 AN: 41526

American (AMR) AF: 0.0615 AC: 940 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 360 AN: 3464

East Asian (EAS) AF: 0.0712 AC: 369 AN: 5182

South Asian (SAS) AF: 0.135 AC: 650 AN: 4828

European-Finnish (FIN) AF: 0.0811 AC: 858 AN: 10584

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0872 AC: 5927 AN: 67954

Other (OTH) AF: 0.0895 AC: 189 AN: 2112

Alfa AF: 0.0868 Hom.: 312

Bravo AF: 0.0823

Asia WGS AF: 0.0850 AC: 296 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.0
DANN	Benign	0.54
PhyloP100		0.18
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: rs7799346; hg19: chr7-33312020;