7-33202862-T-G

Position:

• chr7-33202862-T-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+25271T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 152,184 control chromosomes in the GnomAD database, including 2,942 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 (2942 hom., cov: 32)
• Consequence: BBS9 NM_198428.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0670

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BBS9	NM_198428.3	c.442+25271T>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+25271T>G		intron_variant		1	NM_198428.3	ENSP00000242067.6

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28915 AN: 152066 Hom.: 2939 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.347

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.190 AC: 28929 AN: 152184 Hom.: 2942 Cov.: 32 AF XY: 0.185 AC XY: 13740 AN XY: 74400

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.162

Gnomad4 EAS AF: 0.163

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.189

Gnomad4 NFE AF: 0.233

Gnomad4 OTH AF: 0.175

Alfa AF: 0.215 Hom.: 4810

Bravo AF: 0.183

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.6
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: rs10486524; hg19: chr7-33242474;