rs10486523

Positions:

• chr7-33202384-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198428.3(BBS9):​c.442+24793C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0826 in 152,216 control chromosomes in the GnomAD database, including 557 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 0.083 (557 hom., cov: 32)
• Consequence: BBS9 NM_198428.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.331

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BBS9	NM_198428.3	c.442+24793C>T		intron_variant		ENST00000242067.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BBS9	ENST00000242067.11	c.442+24793C>T		intron_variant		1	NM_198428.3	P3

Frequencies

GnomAD3 genomes AF: 0.0827 AC: 12574 AN: 152098 Hom.: 557 Cov.: 32

Gnomad AFR AF: 0.0753

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.0619

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.0749

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.0806

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0876

Gnomad OTH AF: 0.0926

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

GnomAD4 genome AF: 0.0826 AC: 12580 AN: 152216 Hom.: 557 Cov.: 32 AF XY: 0.0824 AC XY: 6130 AN XY: 74420

Gnomad4 AFR AF: 0.0752

Gnomad4 AMR AF: 0.0618

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.0751

Gnomad4 SAS AF: 0.136

Gnomad4 FIN AF: 0.0806

Gnomad4 NFE AF: 0.0876

Gnomad4 OTH AF: 0.0917

Alfa AF: 0.0873 Hom.: 814

Bravo AF: 0.0827

Asia WGS AF: 0.0860 AC: 301 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.9
DANN	Benign	0.29

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

Publications

LitVar

Other links and lift over

dbSNP: rs10486523; hg19: chr7-33241996;