7-33467033-T-C

Variant names:

• chr7-33467033-T-C
• rs4509212
• NM_198428.3:c.2116-38430T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_198428.3(BBS9):​c.2116-38430T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.47 (3298 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: BBS9 NM_198428.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.98
• Publications: 6 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BBS9	NM_198428.3	c.2116-38430T>C		intron_variant	Intron 19 of 22	ENST00000242067.11	NP_940820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BBS9	ENST00000242067.11	c.2116-38430T>C		intron_variant	Intron 19 of 22	1	NM_198428.3	ENSP00000242067.6

Frequencies

GnomAD3 genomes AF: 0.466 AC: 31349 AN: 67284 Hom.: 3294 Cov.: 0

Gnomad AFR AF: 0.513

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.521

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.483

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.466 AC: 31371 AN: 67338 Hom.: 3298 Cov.: 0 AF XY: 0.469 AC XY: 15157 AN XY: 32320

African (AFR) AF: 0.513 AC: 7918 AN: 15436

American (AMR) AF: 0.489 AC: 3039 AN: 6218

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 684 AN: 1688

East Asian (EAS) AF: 0.455 AC: 1008 AN: 2214

South Asian (SAS) AF: 0.482 AC: 992 AN: 2058

European-Finnish (FIN) AF: 0.470 AC: 2169 AN: 4618

Middle Eastern (MID) AF: 0.538 AC: 70 AN: 130

European-Non Finnish (NFE) AF: 0.444 AC: 14944 AN: 33676

Other (OTH) AF: 0.483 AC: 453 AN: 938

Alfa AF: 0.679 Hom.: 44798

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.19
DANN	Benign	0.62
PhyloP100		-2.0
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: rs4509212; hg19: chr7-33506645;