rs10486525

chr7-33280829-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.1016+6873C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 149,778 control chromosomes in the GnomAD database, including 1,131 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 0.11 (1131 hom., cov: 31)
• Consequence: BBS9 NM_198428.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.163

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BBS9	NM_198428.3	c.1016+6873C>T		intron_variant		ENST00000242067.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BBS9	ENST00000242067.11	c.1016+6873C>T		intron_variant		1	NM_198428.3	P3

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17006 AN: 149682 Hom.: 1127 Cov.: 31

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.0813

Gnomad AMR AF: 0.0735

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.0718

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.0836

Gnomad MID AF: 0.0960

Gnomad NFE AF: 0.0876

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.114 AC: 17029 AN: 149778 Hom.: 1131 Cov.: 31 AF XY: 0.112 AC XY: 8199 AN XY: 72928

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.0734

Gnomad4 ASJ AF: 0.104

Gnomad4 EAS AF: 0.0720

Gnomad4 SAS AF: 0.136

Gnomad4 FIN AF: 0.0836

Gnomad4 NFE AF: 0.0876

Gnomad4 OTH AF: 0.115

Alfa AF: 0.0994 Hom.: 121

Bravo AF: 0.118

Asia WGS AF: 0.0920 AC: 320 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	2.9
Dann	Benign	0.51

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: rs10486525; hg19: chr7-33320441;