rs12374818

Variant names:

• chr7-33654496-G-A
• rs12374818
• ENST00000672453.1:n.2476+48764G>A

Variant summary

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

The ENST00000672453.1(BBS9):​n.2476+48764G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0455 in 152,154 control chromosomes in the GnomAD database, including 193 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 0.045 (193 hom., cov: 32)
• Consequence: BBS9 ENST00000672453.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.486
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0513 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.2476+48764G>A		intron_variant	Intron 20 of 22

Frequencies

GnomAD3 genomes AF: 0.0455 AC: 6914 AN: 152036 Hom.: 193 Cov.: 32

Gnomad AFR AF: 0.0349

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.0521

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0332

Gnomad FIN AF: 0.0229

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0527

Gnomad OTH AF: 0.0512

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

GnomAD4 genome AF: 0.0455 AC: 6923 AN: 152154 Hom.: 193 Cov.: 32 AF XY: 0.0443 AC XY: 3297 AN XY: 74386

African (AFR) AF: 0.0351 AC: 1456 AN: 41510

American (AMR) AF: 0.0521 AC: 796 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 359 AN: 3470

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5182

South Asian (SAS) AF: 0.0333 AC: 160 AN: 4812

European-Finnish (FIN) AF: 0.0229 AC: 242 AN: 10580

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.0527 AC: 3586 AN: 67994

Other (OTH) AF: 0.0507 AC: 107 AN: 2112

Alfa AF: 0.0471 Hom.: 20

Bravo AF: 0.0472

Asia WGS AF: 0.0160 AC: 55 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.70
DANN	Benign	0.54
PhyloP100		-0.49

Splicing

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

Other links and lift over

dbSNP: rs12374818; hg19: chr7-33694108;