rs10486521

Positions:

• chr7-33198588-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_198428.3(BBS9):​c.442+20997A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,000 control chromosomes in the GnomAD database, including 1,125 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 0.10 (1125 hom., cov: 32)
• Consequence: BBS9 NM_198428.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.34

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BBS9	NM_198428.3	c.442+20997A>G		intron_variant		ENST00000242067.11	NP_940820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BBS9	ENST00000242067.11	c.442+20997A>G		intron_variant		1	NM_198428.3	ENSP00000242067	P3

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15537 AN: 151880 Hom.: 1125 Cov.: 32

Gnomad AFR AF: 0.0278

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.0772

Gnomad ASJ AF: 0.0923

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0350

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.0806

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

GnomAD4 genome AF: 0.102 AC: 15537 AN: 152000 Hom.: 1125 Cov.: 32 AF XY: 0.0985 AC XY: 7323 AN XY: 74318

Gnomad4 AFR AF: 0.0277

Gnomad4 AMR AF: 0.0772

Gnomad4 ASJ AF: 0.0923

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0350

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.0798

Alfa AF: 0.138 Hom.: 2115

Bravo AF: 0.0923

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	13
DANN	Benign	0.81

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: rs10486521; hg19: chr7-33238200;