rs10486523

Variant names:

• chr7-33202384-C-T
• rs10486523
• NM_198428.3:c.442+24793C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-0.92).
• 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 rank	MANE	Protein	UniProt
BBS9	NM_198428.3	c.442+24793C>T		intron_variant	Intron 5 of 22	ENST00000242067.11	NP_940820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BBS9	ENST00000242067.11	c.442+24793C>T		intron_variant	Intron 5 of 22	1	NM_198428.3	ENSP00000242067.6

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

African (AFR) AF: 0.0752 AC: 3123 AN: 41534

American (AMR) AF: 0.0618 AC: 945 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 363 AN: 3468

East Asian (EAS) AF: 0.0751 AC: 389 AN: 5182

South Asian (SAS) AF: 0.136 AC: 657 AN: 4824

European-Finnish (FIN) AF: 0.0806 AC: 854 AN: 10590

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0876 AC: 5954 AN: 68006

Other (OTH) AF: 0.0917 AC: 194 AN: 2116

Alfa AF: 0.0869 Hom.: 1020

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
PhyloP100		-0.33
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10486523; hg19: chr7-33241996;