chr7-33633653-G-T

Variant names:

• chr7-33633653-G-T
• rs17170316
• NM_001348041.4:c.2633-1524G>T

Variant summary

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

The NM_001348041.4(BBS9):​c.2633-1524G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0641 in 151,970 control chromosomes in the GnomAD database, including 1,001 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 0.064 (1001 hom., cov: 31)
• Consequence: BBS9 NM_001348041.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.267
• 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: 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001348041.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBS9	NM_001348041.4		c.2633-1524G>T		intron	N/A	NP_001334970.1
	BBS9	NM_001362679.1		c.2522-1524G>T		intron	N/A	NP_001349608.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBS9	ENST00000673056.1		c.2633-1524G>T		intron	N/A	ENSP00000499989.1
	BBS9	ENST00000671952.1		c.2522-1524G>T		intron	N/A	ENSP00000500239.1
	BBS9	ENST00000672453.1		n.2476+27921G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0640 AC: 9712 AN: 151856 Hom.: 984 Cov.: 31

Gnomad AFR AF: 0.0146

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.0424

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.0575

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0326

Gnomad OTH AF: 0.0617

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

GnomAD4 genome AF: 0.0641 AC: 9748 AN: 151970 Hom.: 1001 Cov.: 31 AF XY: 0.0723 AC XY: 5373 AN XY: 74286

African (AFR) AF: 0.0146 AC: 604 AN: 41462

American (AMR) AF: 0.218 AC: 3331 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0424 AC: 147 AN: 3470

East Asian (EAS) AF: 0.401 AC: 2064 AN: 5150

South Asian (SAS) AF: 0.129 AC: 618 AN: 4806

European-Finnish (FIN) AF: 0.0575 AC: 605 AN: 10522

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0326 AC: 2218 AN: 67964

Other (OTH) AF: 0.0672 AC: 142 AN: 2114

Alfa AF: 0.0474 Hom.: 2307

Bravo AF: 0.0754

Asia WGS AF: 0.270 AC: 936 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.3
DANN	Benign	0.64
PhyloP100		-0.27

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17170316; hg19: chr7-33673265;