rs10272438

Positions:

• chr7-33199222-A-G

Variant summary

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

The NM_198428.3(BBS9):​c.442+21631A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 151,842 control chromosomes in the GnomAD database, including 3,525 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 0.19 (3525 hom., cov: 32)
• Consequence: BBS9 NM_198428.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.290

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BBS9	NM_198428.3	c.442+21631A>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+21631A>G		intron_variant		1	NM_198428.3	ENSP00000242067	P3

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28339 AN: 151724 Hom.: 3520 Cov.: 32

Gnomad AFR AF: 0.0494

Gnomad AMI AF: 0.217

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.0333

Gnomad SAS AF: 0.0882

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.215

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

GnomAD4 genome AF: 0.187 AC: 28352 AN: 151842 Hom.: 3525 Cov.: 32 AF XY: 0.191 AC XY: 14151 AN XY: 74204

Gnomad4 AFR AF: 0.0493

Gnomad4 AMR AF: 0.336

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.0336

Gnomad4 SAS AF: 0.0880

Gnomad4 FIN AF: 0.261

Gnomad4 NFE AF: 0.242

Gnomad4 OTH AF: 0.213

Alfa AF: 0.217 Hom.: 604

Bravo AF: 0.188

Asia WGS AF: 0.0640 AC: 224 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.47
DANN	Benign	0.78

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: rs10272438; hg19: chr7-33238834;