rs1362927

Variant names:

• chr7-33777097-G-A
• rs1362927
• ENST00000672453.1:n.2477-4661G>A

Variant summary

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

The ENST00000672453.1(BBS9):​n.2477-4661G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.79 in 152,060 control chromosomes in the GnomAD database, including 48,085 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 0.79 (48085 hom., cov: 31)
• Consequence: BBS9 ENST00000672453.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.623
• Publications: 5 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.836 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BBS9	ENST00000672453.1	n.2477-4661G>A		intron_variant	Intron 20 of 22

Frequencies

GnomAD3 genomes AF: 0.790 AC: 120038 AN: 151942 Hom.: 48077 Cov.: 31

Gnomad AFR AF: 0.801

Gnomad AMI AF: 0.945

Gnomad AMR AF: 0.652

Gnomad ASJ AF: 0.859

Gnomad EAS AF: 0.523

Gnomad SAS AF: 0.706

Gnomad FIN AF: 0.733

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.842

Gnomad OTH AF: 0.812

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

GnomAD4 genome AF: 0.790 AC: 120076 AN: 152060 Hom.: 48085 Cov.: 31 AF XY: 0.778 AC XY: 57793 AN XY: 74322

African (AFR) AF: 0.801 AC: 33189 AN: 41452

American (AMR) AF: 0.651 AC: 9949 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.859 AC: 2984 AN: 3472

East Asian (EAS) AF: 0.523 AC: 2684 AN: 5136

South Asian (SAS) AF: 0.707 AC: 3403 AN: 4814

European-Finnish (FIN) AF: 0.733 AC: 7761 AN: 10588

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.842 AC: 57272 AN: 68006

Other (OTH) AF: 0.806 AC: 1703 AN: 2114

Alfa AF: 0.821 Hom.: 219345

Bravo AF: 0.783

Asia WGS AF: 0.575 AC: 2007 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.59
DANN	Benign	0.61
PhyloP100		-0.62

Splicing

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

Other links and lift over

dbSNP: rs1362927; hg19: chr7-33816709;